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Normal physiology (brief overview)
Abstract
Puberty is a defining phase of human development where growth ends and the ability to reproduce begins. An understanding of the events leading up to puberty highlights the fact that this is the culmination of a process of skeletal and gonadal activity that has been ongoing since conception. Although there is natural variation in the timing of events in and around puberty the basic underlying processes are common to all healthy human beings. This chapter is intended to outline the mechanisms underlying normal growth and development before and during puberty. By understanding normality the pathological processes that give rise to abnormalities of pubertal development can be understood more easily.
... In puberty there are two main events, namely, activation of the gonads by follicle stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary, this is called gonadarche. In addition to gonadarche, there is also adrenarche which is an increase in androgen production by the adrenal cortex (Fadila &;Nugroho, 2018;Wood et al., 2019). ...
... This assessment describes systematically secondary sex growth such as breast growth (telarche) in women, genital growth in males, and pubarche hair growth (pubarche) in both. Changes in these three things are described in 5 stages, the first stage describes the prepubertal phase, while the fifth stage describes adult growth (Calcaterra et al., 2021;Wood et al., 2019). ...
... It is important in the history to know the age of puberty of the parents, the onset of puberty in the child, the possibility of steroid exposure, and signs of the occurrence of lesions in the CNS. A thorough physical examination should focus on antopometric examination and secondary sex assessment using the Marshall and Tanner classification (Wood et al., 2019). Teddy Tjahyanto, Eunike Angellina Mulyadi, Gabriel Angelica Novian, Louis Rianto/ ...
Introduction: Exclusive breastfeeding is breast milk given without other foods to children up to 6 months of age. Breast milk has many uses, including helping children's growth and development, preventing infections, reducing the risk of obesity, and helping children's mental and psychomotor development. Exclusive breastfeeding was found to have a protective effect against the incidence of precocious puberty. Precocious puberty is defined as the onset of puberty that occurs before age 8 in girls and age 9 in boys. Objective: Based on these findings, the authors want to make a study to compile the latest research results on the association of exclusive breastfeeding as one of the prevention of precocious puberty. Method: The author searches, selects, and selects journals related to exclusive breastfeeding with the prevention of precocious puberty through several research databases including ScienceDirect, Google Scholar, PubMed, and Wiley. The keywords used are "exclusive breastfeeding", "precocious puberty", and "prevention". Results and discussion: Various studies have shown that exclusive breastfeeding has a protective effect against the incidence of precocious puberty. Exclusive breastfeeding alone can reduce the risk of obesity in children. Obesity in this child, based on several studies, is a risk factor for precocious puberty. Conclusion: Exclusive breastfeeding of children can prevent the incidence of precocious puberty.
... Puberty begins with the activation of hypothalamic-pituitary-gonadal axis (HPG), which already occurs during fetal life, but is usually silenced in the final period of pregnancy and then reactivated immediately after birth [5,6]. This post-natal transitory activation is defined as minipuberty and lasts up to 6 months in boys and up to 2 years in girls, until the blockage of gonadotropinreleasing hormone (GnRH) secretion, which will resume during puberty [7,8]. ...
... Regardless of the cause, PP must be promptly recognized since it is associated with accelerated stature growth and skeletal maturation if untreated, inducing an early growth arrest with premature epiphyseal fusion due to excess sex steroids, which results in short adult height [2]. The key features suggesting PP are the progressive development of breasts in girls and testicular volume in boys over a short period of observation (3-6 months) associated with rapid height growth (height velocity 6-7 cm/year ) especially in girls aged between 6-8 years, when this condition occurs more frequently [5,31,32]. ...
... Growth spurt is an important feature of pubertal development. In fact, growth acceleration with growth centile change supports the diagnosis of pubertal activation and therefore of PP [5,26]. ...
Puberty identifies the transition from childhood to adulthood. It normally lasts from 3 to 5 years and begins from 9 years in males and 8 years in females, although with differences related to familiarity and geographical origin. Precocious puberty is the onset of signs of pubertal development before age 8 in girls and before age 9 in boys, it has an incidence of 1/5000–1/10.000 with an F:M ratio ranging from 3:1 to 20:1. Based on the mechanism that triggers puberty, precocious puberty can be classified as central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also known as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual characteristics, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analogs therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.
... Puberty represents the process of physical maturation where an adolescent reaches sexual maturity. There is a very wide variation in the age range of the onset of puberty, which depends on genetic, familial, ethnic, nutritional, environmental, and socioeconomic factors [5]. Although the factors underlying the individual differences in pubertal timing have not been completely identified, evidence shows that the activation of HPG depends on both genetics and environment [5]. ...
... There is a very wide variation in the age range of the onset of puberty, which depends on genetic, familial, ethnic, nutritional, environmental, and socioeconomic factors [5]. Although the factors underlying the individual differences in pubertal timing have not been completely identified, evidence shows that the activation of HPG depends on both genetics and environment [5]. ...
... The gonadotropinreleasing hormone (GnRH) pulsatile secretion from the hypothalamus starts to increase and promotes the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary gland. The FSH and, in particular, the LH secretion increase in frequency and amplitude, stimulating the release of steroid hormones and gametogenesis in the gonads [5]. ...
Pubertal development represents the process of physical maturation where an adolescent reaches sexual maturity and attains reproductive function. The effects of vitamin D are mainly mediated by the vitamin D receptor (VDR), which is expressed in almost all body cells, including the ovary and human pituitary gland and animal hypothalamus. Thus, vitamin D has gained great interest as pathogenic factor of pubertal disorders and fertility. This narrative review aimed to provide a broad overview of the available literature regarding the association between vitamin D levels, puberty timing, and age at menarche. A review of the data on the involvement of micronutrient deficiency, as a modifiable cause of pubertal disorders, is important for the prediction and prevention of deficiencies as well as for fertility protection and should be considered a public health priority. Reported data support that vitamin D is a regulator of neuroendocrine and ovarian physiology and, more in detail, a deficiency of vitamin D is involved in altered pubertal timing. Considering the long-term consequences of early pubertal development and early menarche, the detection of modifiable causes is crucial in preventive strategies. Future studies in humans and with an increased scale are needed to elucidate the vitamin D role in sexual maturation and puberty development.
... Puberty is a complex physiological process of developmental changes regulated by multiple genetic and hormonal pathways. During puberty, adolescents reach sexual maturity and become capable of reproduction [36]. Luteinizing hormone (LH) and follicular stimulating hormone (FSH) are released from the pituitary gland in a pulsatile manner in response to hypothalamic gonadotrophin-releasing hormone (GnRH) stimulation. ...
... Luteinizing hormone (LH) and follicular stimulating hormone (FSH) are released from the pituitary gland in a pulsatile manner in response to hypothalamic gonadotrophin-releasing hormone (GnRH) stimulation. The number and amplitude of pulses increase at puberty, and there is an augmentation in the production of sex steroid hormones, primarily estrogens in girls and androgens in boys [36]. Puberty onset usually occurs after 8 years of age (range 8-13 years) in girls, and the development of breast tissue (Tanner staging B2) is its clinical marker. ...
... Puberty onset usually occurs after 8 years of age (range 8-13 years) in girls, and the development of breast tissue (Tanner staging B2) is its clinical marker. In boys, a testicular volume greater than 4 mL is the marker of puberty onset, between 9 and 14 years of age [36]. The pubertal spurt commonly starts at B2 in girls and at a testicular volume of around 10 mL in boys [36]. ...
Longitudinal growth and puberty are the result of a complex interaction of genetic, hormonal, nutritional, and environmental factors. Acne vulgaris is a chronic disease of the pilosebaceous unit that affects 85% of adolescents worldwide. Isotretinoin is a synthetic vitamin A derivative drug effective and is widely employed for the treatment of moderate and severe acne vulgaris. Premature epiphyseal closure has been reported in patients with neuroblastoma treated with high doses of isotretinoin as well as in patients with acne receiving lower doses. Although the mechanisms for these effects are not clear, it has been suggested that isotretinoin may have a negative impact on the GH-IGF-I axis, leading to a reduction in IGF-I and IGFBP3 serum levels. Although many of the isotretinoin adverse effects in pediatric patients are transient, premature epiphyseal closure and bone abnormalities can lead to transient abnormalities and permanent deformities with a negative impact on longitudinal growth and final height. The aim of this study was to review the potential effects of oral isotretinoin on the growth plate and growth during childhood and adolescence.
... (LH), which in turn promotes the release of sex hormones (e.g., testosterone) from the gonads, which have negative feedback to both the pituitary and hypothalamus (Wood et al., 2019; Figure 2). The onset of production of adult-typical circulating concentrations of these hormones is a defining feature of sexual maturation. ...
... Puberty is triggered by large increases in pulsatile GnRH, which leads to large downstream increases in sex hormones (Witchel & Topaloglu, 2019 About 50-80% of pubertal timing is believed to be genetically determined, with the remainder due to environmental influences (Wood et al., 2019). The onset of puberty thus represents an interplay between genetics and an organism's current and past socioecological experiences (Stephens & Wallen, 2013). ...
Developmental plasticity is particularly important for humans and other primates because of our extended period of growth and maturation, during which our phenotypes adaptively respond to environmental cues. The hypothalamus-pituitary-gonadal (HPG) and hypothalamus-pituitary-adrenal (HPA) axes are likely to be principal targets of developmental "programming" given their roles in coordinating fitness-relevant aspects of the phenotype, including sexual development, adult reproductive and social strategies, and internal responses to the external environment. In social animals, including humans, the social environment is believed to be an important source of cues to which these axes may adaptively respond. The effects of early social environments on the HPA axis have been widely studied in humans, and to some extent, in other primates, but there are still major gaps in knowledge specifically relating to males. There has also been relatively little research examining the role that social environments play in developmental programming of the HPG axis or the HPA/HPG interface, and what does exist disproportionately focuses on females. These topics are likely understudied in males in part due to the difficulty of identifying developmental milestones in males relative to females and the general quiescence of the HPG axis prior to maturation. However, there are clear indicators that early life social environments matter for both sexes. In this review, we examine what is known about the impact of social environments on HPG and HPA axis programming during male development in humans and nonhuman primates, including the role that epigenetic mechanisms may play in this programming. We conclude by highlighting important next steps in this research area. K E Y W O R D S developmental programming, hypothalamus-pituitary-adrenal axis, hypothalamus-pituitary-gonadal axis, male primates, social environment
... During human development, it is not known whether motoneuron PICs also increase in amplitude and decrease in recruitment threshold in the first few weeks and months after birth or whether there are continual changes from preadolescence to adulthood. To address the latter question, we used the simultaneous firing behaviour of multiple motor units from the tibialis anterior (TA) muscle to indirectly examine the potential contribution of motoneuron PICs to self-sustained firing in participants between the ages of 7-17 years in the preadolescent and adolescent stages (Brix et al., 2019;Wood et al., 2019) and during young adulthood (18-28 years of age). These two groups were also compared to an adult group (32-53 years) before appreciable motor unit loss (McNeil et al., 2005) or decreases in self-sustained firing of motor units (Hassan et al., 2021;Orssatto et al., 2021). ...
... Hormones, such as oestradiol and testosterone, facilitate the maturation of inhibitory GABAergic signalling (Gilfarb & Leuner, 2022). Because these hormones increase during the young development period (Barrientos et al., 2019;Wood et al., 2019), increases in the excitability of inhibitory circuitry may contribute to the age-related decrease in self-sustained firing we observed in this study. We did not measure whether participants in the young development group were before, within or after puberty, to determine whether motoneuron PICs changed in direct relation to predicted changes in sex hormones. ...
Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age‐related development of self‐sustained firing and general excitability of tibialis anterior motoneurons in a young development (7–17 years), young adult (18–28 years) and adult (32–53 years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11–28 years). Self‐sustained firing, as measured by ΔF, was larger in the young development (∼5.8 Hz, n = 20) compared to the young adult (∼4.9 Hz, n = 13) and adult (∼4.8 Hz, n = 8) groups, consistent with a developmental decrease in self‐sustained firing mediated by persistent inward currents (PIC). ΔF was also larger in participants taking SSRIs (∼6.5 Hz, n = 9) compared to their age‐matched controls (∼5.3 Hz, n = 26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. Participants in the young development and SSRI groups also had higher firing rates and a steeper acceleration in initial firing rates (secondary ranges), consistent with the PIC producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the adults, which, in the young development group, was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge which vary during development, with a time course similar to the changes in motoneuron firing behaviour observed in the present study. image
Key points
Neurons in the spinal cord that activate muscles in the limbs (motoneurons) undergo increases in excitability shortly after birth to help animals stand and walk.
We examined whether the excitability of human ankle flexor motoneurons also continues to change from child to adulthood by recording the activity of the muscle fibres they innervate.
Motoneurons in children and adolescents aged 7–17 years (young development group) had higher signatures of excitability that included faster firing rates and more self‐sustained activity compared to adults aged ≥18 years.
Participants aged 11–28 years of age taking serotonin reuptake inhibitors had the highest measures of motoneuron excitability compared to their age‐matched controls.
The young development group also had more unstable contractions, which might partly be related to the high excitability of the motoneurons.
... The increase in amplitude of LH and FSH secretion, causes a greater production of steroid sex hormones, primarily estrogens. The rise in gonadal sex steroid production, following Gn stimulation, is responsible for changes in many tissues, including the genitals, skin, breast, bone etc. (1,2). ...
... In the vast majority of teenage girls, the first symptom of puberty is the enlargement of the mammary glands -thelarche, followed by an acceleration of the skeletal growth rate, the development of pubic hair -pubarche and the appearance of the first menstruation -menarche (1,2). The increasing frequency of pulsatile gonadoliberin release is a necessary condition for the initiation of puberty. ...
Precocious puberty is diagnosed when pubertal characteristics appear before the age of 8 years in females. The most common form is gonadotropin-dependent, called axial. The primary method of treatment is administration of gonadotrophin-releasing hormone analogues (GnRHa). The aim of the study was to verify hypothesis that GnRHa therapy in the childhood may be of additive risk factor for polycystic ovary syndrome (PCOS) in adulthood.
Material and Methods
The study group consists of 24 women (median age 22 88 years, median BMI 23.5) treated with GnRHa for central precocious puberty in childhood. The control group includes 40 women (median age 23 years, median BMI 25.6) diagnosed with isolated premature thelarche and not using GnRHa in the childhood. Anthropometric measurements, ultrasound examination of minor pelvis and hormonal profile were performed. PCOS diagnosis was based on Rotterdam criteria.
Results
The study confirmed a higher prevalence of PCOS in the study group (50%) than in the control group (10%); p=0.0006. Significant, linear correlation between free testosterone levels and ovarian size was found in the study group (R=0.45 p= 0.03).
Conclusions
GnRHa therapy during childhood may have a potential influence on incidence of PCOS in the adulthood. Therefore, in this group of patients long-term follow-up focused on screening for PCOS would seem beneficial.
... Regardless of the cause, PP must be promptly recognized since it is associated with accelerated stature growth and skeletal maturation if untreated, inducing an early growth arrest with premature epiphyseal fusion due to excess sex steroids, which sometimes results in short adult height [2]. The key features suggesting PP are the progressive development of breasts in girls and testicular volume in boys over a short period of observation (3-6 months) associated with rapid height growth (height velocity >6-7 cm/year) especially in girls aged between 6 and 8 years, when this condition occurs more frequently [5,31,32]. ...
... Growth spurt is an important feature of pubertal development. In fact, growth acceleration with growth centile change supports the diagnosis of pubertal activation and therefore of PP [5,26]. ...
Puberty identifies the transition from childhood to adulthood. Precocious puberty is the onset of signs of pubertal development before age eight in girls and before age nine in boys, it has an incidence of 1/5000–1/10,000 with an F:M ratio ranging from 3:1 to 20:1. Precocious puberty can be divided into central, also known as gonadotropin-dependent precocious puberty or true precocious puberty, and peripheral, also recognized as gonadotropin-independent precocious puberty or precocious pseudopuberty. Thus, the main aim of this narrative report is to describe the standard clinical management and therapy of precocious puberty according to the experience and expertise of pediatricians and pediatric endocrinologists at Policlinico Umberto I, Sapienza University of Rome, Italy. In the suspicion of early sexual maturation, it is important to collect information regarding the age of onset, the speed of maturation of secondary sexual features, exposure to exogenous sex steroids and the presence of neurological symptoms. The objective examination, in addition to the evaluation of secondary sexual characteristics, must also include the evaluation of auxological parameters. Initial laboratory investigations should include serum gonadotropin levels (LH and FSH) and serum levels of the sex steroids. Brain MRI should be performed as indicated by the 2009 Consensus Statement in all boys regardless of chronological age and in all girls with onset of pubertal signs before 6 years of age. The gold standard in the treatment of central precocious puberty is represented by GnRH analogs, whereas, as far as peripheral forms are concerned, the triggering cause must be identified and treated. At the moment there are no reliable data establishing the criteria for discontinuation of GnRH analog therapy. However, numerous pieces of evidence suggest that the therapy should be suspended at the physiological age at which puberty occurs.
... In addition, high blood estrogen concentrations have direct effects on epiphyses and indirectly stimulate an increase in pulsatile secretion of growth hormone (GH) by the pituitary gland, which causes increases in bone mineral content and skeletal muscle mass [24]. However, estrogen has a bidirectional effect on bone growth: at a low concentration, it accelerates osteogenesis in the cartilage through activation of the growth hormone/insulin-like growth factor-1 axis, which increases the linear growth [25]; whereas when present at a high concentration during late puberty, it binds to receptors in growth plates, promoting epiphyseal closure [26]. Another characteristic change during adolescence is a rapid increase in FM, mainly in the chest, abdomen, and hips, which makes the bodies of girls rounder, and their body composition gradually approach those of adults [25]. ...
... However, estrogen has a bidirectional effect on bone growth: at a low concentration, it accelerates osteogenesis in the cartilage through activation of the growth hormone/insulin-like growth factor-1 axis, which increases the linear growth [25]; whereas when present at a high concentration during late puberty, it binds to receptors in growth plates, promoting epiphyseal closure [26]. Another characteristic change during adolescence is a rapid increase in FM, mainly in the chest, abdomen, and hips, which makes the bodies of girls rounder, and their body composition gradually approach those of adults [25]. ...
Background
We aimed to analyze the characteristics of the body composition of children and adolescents aged 3–17 in Suzhou, China.
Methods
A cross-sectional study between January 2020 and June 2022 using bioelectrical impedance was conducted to determine the fat mass (FM), fat-free mass (FFM), skeletal muscle mass, and protein and mineral contents of 24,845 children aged 3–17 who attended the Department of Child and Adolescent Healthcare, Children’s Hospital of Soochow University, China. Measurement data was presented in tables as mean ± SD, and groups were compared using the independent samples t-test.
Results
FM and fat-free mass increased with age in both boys and girls. The fat-free mass of girls aged 14–15 decreased after reaching a peak, and that of boys in the same age group was higher than that of the girls (p < 0.05). There were no significant differences in FM between boys and girls younger than 9- and 10-years old. The percentage body fat (PBF) and FM index of girls increased rapidly between 11 and 15 years of age (p < 0.05), and those of boys aged 11–14 were significantly lower (p < 0.05), suggesting that the increase in body mass index (BMI) was mainly contributed by muscle mass (MM) in boys.
Conclusions
The body composition of children and adolescents varies according to their age and sex. A misdiagnosis of obesity made on the basis of BMI alone can be avoided if BMI is used in combination with FM index, percentage body fat, and other indexes.
... In the males these two stages can be summarized as follows [115]: ...
... • Tanner III: testicular volume between 6 and 12 ml; scrotum enlarges further; penis begins to lengthen, hair becomes more coarse and curly and begins to extend laterally. In the females the two stages of Tanner can be described as follows [115]: ...
Gender dysphoria is a clinical condition characterized by significant distress due to the discordance between biological sex and gender identity. Currently, gender dysphoria is also found more frequently in children and adolescents, thanks to greater social sensibleness and new therapeutic possibilities. In fact, it is estimated that the prevalence of gender dysphoria in pediatric age is between 0.5% and 2% based on the statistics of the various countries. Therefore, the pediatrician cannot fail to update himself on these issues and above all should be the reference figure in the management of these patients. Even if the patient must be directed to a referral center and be followed up by a multidisciplinary team, the treating pediatrician will care to coordinate the clinical and therapeutic framework. The aim of the present report is therefore to integrate literature data with our clinical experience to propose a new clinical approach in which the pediatrician should be the reference in the care of these patients, directing them towards the best therapeutic approach and staying in contact with the specialists of the referral center.
Supplementary Information
The online version contains supplementary material available at 10.1186/s13052-023-01466-z.
... The increase in pulsatile release of gonadotropin-releasing hormone by hypothalamic neurons is a crucial trigger for the onset of puberty and the subsequent physical and hormonal changes that occur during this stage of development.This hormone subsequently stimulates the pituitary gland to release gonadotropins, leading to the maturation of the gonads. [7] ...
Background: Studies have shown that acute exercise alters the expression of circulating neutrophil and peripheral blood mononuclear cell (PBMC) genes, affecting a wide range of processes from cellular growth to the promotion of inflammatory and anti-inflammatory responses.In this study, we identified differential gene expression associated with acute exercise and PBMC in puberty children through the GEO database. We utilized bioinformatics technology to analyze the impact of acute exercise on PBMC and identified key genes involving the puberty children.
Methods: Combining two datasets of gene expression, we identified 197 shared differentially expressed genes (DEGs) in PBMC before and after exercise. We conducted pathway analysis of these DEGs and built a gene co-expression network. The identification of hub genes was achieved through the utilization of protein-protein interaction (PPI) networks.
Results: 268 shared DEGs were identified in the GSE11761 dataset in pre- and post-exercise groups, while 352 differential genes were identified between the pre- and post-exercise groups of females in the GSE14642 dataset. A total of 197 shared genes were identified between the two datasets. Seven core genes were identified by MCODE and CytoHubba, namely IL2RB, KLRD1, GZMB, TBX21, PRF1, HAVCR2, and GZMA.
Conclusion: Bioinformatics techniques are effective in screening and analyzing PBMC-associated DECs in children undergoing acute pre- and post-exercise puberty. Microarray analysis of PBMCs in children undergoing puberty can identify molecules that may predict acute exercise responses. This study provides insights for further exploration of the mechanisms and targets of acute exercise on the organism.
... Puberty activates the HPG axis, leading to psychological and physical maturation, accelerated linear growth, the development of secondary sexual characteristics, and gonadal maturation (16). Common factors affecting pubertal development include genetics, environment, diet, and nutrition (17). Among the nutritional factors, vitamin D is very important. ...
Background
The association between 25(OH)D and pubertal timing has not been well studied. The aim of this study was to assess the relationship between 25(OH)D levels and pubertal timing in children.
Methods
Participants aged 6–14 years who had available nutritional and serum sex hormone (total testosterone (TT) and estradiol (E2)) information (n =1318) were included. We conducted a cross-sectional analysis of the associations between 25(OH)D and sex steroid hormones among children in the National Health and Nutrition Examination Survey, 2015–2016. Puberty was indicated by high levels of steroid hormones (TT≥50 ng/dL in men, E2≥20 pg/ml in women) or menarche.
Results
Serum 25(OH)D and pubertal status showed the same trend in both males and females. In the male population, the OR values of serum 25(OH)D between 50 and <75 and ≥75 nmol/L were 0.52 (0.25, 1.08) and 0.64 (0.23, 1.75), respectively, compared with serum 25(OH)D<50 nmol/L. The OR of serum 25(OH)D ≥50 nmol/L compared with <50 nmol/L was 0.54 (0.26, 1.10), and the P value was statistically significant (P=0.048). In the female population, when the serum 25(OH)D concentration was <50 nmol/L, the ORs corresponding to a serum 25(OH)D concentration between 50 and <75 and ≥75 nmol/L were 0.53 (0.29, 0.98) and 0.50 (0.19, 1.30), respectively. The OR of serum 25(OH)D≥50 nmol/L compared with <50 nmol/L was 0.52 (0.19, 0.96), and the P value was statistically significant (P=0.037).
Conclusions
A lower 25(OH)D level was associated with earlier puberty in both girls and boys. There was a negative association between 25(OH)D concentrations and pubertal timing.
... Impaired longitudinal growth and low body weight due to restrictive eating may have long-term health implications beyond the growing years. Children may experience comorbid psychosocial and cognitive disturbances because of malnutrition, including anxiety and depression, along with comorbid eating disorders [11,[28][29][30]. Moreover, malnutrition may have a substantial impact on physiologic functions, such as hormonal pathways (e.g., menarche and menstruation) and bone mass accrual [9]. ...
Background
We aimed to characterize stature in pediatric patients with avoidant/restrictive food intake disorder (ARFID), including associations between body size and nutrient intake and height.
Methods
We conducted a secondary analysis of pre-treatment data from 60 patients diagnosed with ARFID that were collected from the electronic medical record. Anthropometric measurements were converted to age- and sex-specific Z-scores using pediatric CDC growth charts. Spearman correlations were performed to test the relationship between height and weight/BMI Z-scores as well as height Z-score and diet variables.
Results
On average, height (-0.35 ± 1.38), weight (-0.58 ± 1.56), and BMI (-0.56 ± 1.48) Z-scores tended to be lower than what would be expected in a generally healthy pediatric population. Percent of individuals with height, weight, or BMI Z-score < -2.0 was 8%, 20%, and 17%, respectively. BMI (P < 0.05) and weight (P < 0.05) were positively associated with height Z-score. Further, intake of some nutrients (e.g., calcium, vitamin D) correlated positively with height Z-score (all P < 0.05).
Conclusions
The cross-sectional relationships reported in this study suggest that in children with ARFID, body weight and consumption of bone-augmenting nutrients such as calcium and vitamin D correlated with height. A thorough understanding of the clinical manifestations of malnutrition and longitudinal effects of restrictive eating in patients with ARFID is critical.
... The European guideline consensus update suggests that HPGA initiation can be determined when the basal luteinzing hormone (LH) value is greater than 0.83 [23]. However, GnRH provocation test is still required to clarify the type of precocious puberty in most children [24]. However, the results of GnRH stimulation test are affected by obesity and other factors, and false-negative phenomenon may occur in the clinic. ...
Background
To investigate serum irisin levels in girls at different developmental status and explore the significance of irisin for the diagnosis of central precocious puberty (CPP) in girls.
Methods
In this cross-sectional study 111 girls were enrolled, including 43 cases of CPP, 44 cases of peripheral precocious puberty (PPP) and 24 cases of girls with normal sexual development as controls. The data on age, weight and height, measured blood levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and irisin were collected. Pelvic Doppler ultrasound was performed to evaluate uterine length, transverse diameter, anteroposterior diameter. The girls were divided into non-CPP group and CPP group according to gonadotropin-releasing hormone (GnRH) stimulation test.
Results
Serum irisin levels were significantly higher in CPP group than in PPP group and normal control group. Serum irisin level was positively correlated with basal LH level, basal FSH level, peak LH level, peak LH /FSH ratio, uterine volume, bone age, and bone age index. The area under the curve, cut-off value, sensitivity and specificity of serum irisin were 0.958, 219.255 pg/ml, 100% and 80.6%. The combined diagnosis of CPP in girls by serum irisin and serum basal LH combined with uterine volume had an AUC, sensitivity, and specificity of 0.994, 97.6%, and 100%, superior to that of the single index.
Conclusions
Serum irisin level in girls with CPP is significantly increased. An irisin combined index could help the diagnosis of CPP in girls.
... During adolescence, there is a significant change in the levels of hormones, particularly gonadotropic releasing hormone (GnRH), FSH and LH, as well sex gonadal sex steroids that lead to sexual development (37). Certain hormonal developments are unique to sex, such as mammary gland development, which accelerates during puberty. ...
Introduction
Hormones play a vital role in development from conception to birth and throughout the human lifespan. These periods are logically divided into fetal development, pre-pubertal growth, puberty, and adulthood. Deviations from standard physiological levels and release patterns of constituent hormones can lead to pathology affecting the normal developmental trajectory. Research is ongoing to better understand the mechanisms of these hormones and how their modulation affects development.
Methods
This article focuses on recent developments in understanding the role hormones play in development. We also cover recent discoveries in signaling pathways and hormonal regulation.
Results
New and continuing research into functional hormone regulation focuses on sex hormones, gonadotropic hormones, growth hormones, insulin-like growth factor, thyroid hormone, and the interconnectedness of each of these functional axes. Currently, the abundance of work focuses on fertility and correction of sex hormone levels based on an individual’s condition and stage in life.
Discussion
Continuing research is needed to fully understand the long-term effects of hormone modulation in growth and sexual development. The role of each hormone in parallel endocrine axes should also be more thoroughly investigated to help improve the safety and efficacy in endocrine pharmacotherapeutics.
... During physiological puberty, boys grow on average 25-30 cm with a PHV of 9.5 cm/year (Tanner and Davies, 1985;Wood et al., 2019). In a study by Fouatih et al. (2019), a final height within their target height range but below average pubertal growth was reported in nine boys with BTR who received TRT. ...
STUDY QUESTION
What is the long-term outcome of individuals born with bilateral testicular regression (BTR) in relation to its underlying etiology?
SUMMARY ANSWER
Statural growth and pubertal development are adequate with incremental doses of testosterone replacement therapy (TRT); however, penile growth is often suboptimal, especially in those with a suspected genetic etiology (i.e. heterozygous DHX37 variants) or a micropenis at birth.
WHAT IS KNOWN ALREADY
BTR is a rare and poorly understood condition. Although a vascular origin has been postulated, heterozygous missense variants in DHX37 have been attributed to the phenotype as well. How these various etiologies impact the clinical phenotype, gonadal histology and outcome of BTR remains unclear.
STUDY DESIGN, SIZE, DURATION
For this cross-sectional study, individuals with BTR were recruited in eight Belgian pediatric endocrinology departments, between December 2019 and December 2022. A physical exam was performed cross-sectionally in all 17 end-pubertal participants and a quality of care questionnaire was completed by 11 of them. Exome-based panel testing of 241 genes involved in gonadal development and spermatogenesis was performed along with a retrospective analysis of presentation and management. A centralized histological review of gonadal rests was done for 10 participants.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 35 participants (33 with male, 1 with female, and 1 with non-binary gender identity) were recruited at a mean age of 15.0 ± 5.7 years.
MAIN RESULTS AND THE ROLE OF CHANCE
The median age at presentation was 1.2 years [0–14 years]. Maternal gestational complications were common (38.2%), with a notably high incidence of monozygotic twin pregnancies (8.8%). Heterozygous (likely) pathogenic missense variants in DHX37 (p.Arg334Trp and p.Arg308Gln) were found in three participants. No other (likely) pathogenic variants were found. All three participants with a DHX37 variant had a microphallus at birth (leading to female sex assignment in one), while only six of the remaining 31 participants without a DHX37 variant (19.4%) had a microphallus at birth (information regarding one participant was missing). Testosterone therapy during infancy to increase penile growth was more effective in those without versus those with a DHX37 variant. The three participants with a DHX37 variant developed a male, female, and non-binary gender identity, respectively; all other participants identified as males. TRT in incremental doses had been initiated in 25 participants (median age at start was 12.4 years). Final height was within the target height range in all end-pubertal participants; however, 5 out of 11 participants (45.5%), for whom stretched penile length (SPL) was measured, had a micropenis (mean adult SPL: 9.6 ± 2.5). Of the 11 participants who completed the questionnaire, five (45.5%) reported suboptimal understanding of the goals and effects of TRT at the time of puberty induction. Furthermore, only 6 (54.5%) and 5 (45.5%) of these 11 participants indicated that they were well informed about the risks and potential side effects of TRT, respectively. Histological analysis of two participants with DHX37 variants suggested early disruption of gonadal development due to the presence of Müllerian remnants in both and undifferentiated gonadal tissue in one. In eight other analyzed participants, no gonadal remnants were found, in line with the BTR diagnosis.
LIMITATIONS, REASONS FOR CAUTION
The limitations of this study include the relatively small sample size (n = 35) and the few individuals with DHX37 variants (n = 3). Furthermore, data on the SPL were often missing, due to this being undocumented or refused by participants.
WIDER IMPLICATIONS OF THE FINDINGS
TRT provides adequate statural growth, even when initiated in late adolescence, thus providing time for physicians to explore the patients’ gender identity if needed. However, sufficient and understandable information regarding the effects and side effects of TRT is required throughout the management of these patients. SPL remains suboptimal in many individuals and could be improved by TRT during infancy to mimic the physiological mini-puberty. An environmental origin in some participants is supported by the high incidence of gestational complications (38.2%) and by the three monozygotic twin pregnancies discordant for the BTR phenotype. Individuals with a heterozygous DHX37 variant have a more severe phenotype with severely restricted penile growth until adulthood. Histological analysis confirmed DHX37 as a gonadal development, rather than a BTR-related, gene.
STUDY FUNDING/COMPETING INTEREST(S)
Funding was provided by the Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED) and by Ghent University Hospital under the NucleUZ Grant (E.D.B.). M.C. and E.D.B. are supported by an FWO senior clinical investigator grant (1801018N and 1802220N, respectively). The authors report no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
... Puberty is a transitional period from childhood to adulthood that is characterized by the maturation of secondary sexual characteristics and the onset of reproductive capabilities [1,2]. The timing of puberty can be affected by various factors, such as genetics, ethnicity, climate, geographical environment, nutrition, and sleep duration [3][4][5][6]. ...
Study Objectives
Evidence implied that sleeping duration is associated with the timing of puberty and that sleep deprivation triggers early pubertal onset in adolescents. Sleep deprivation can affect metabolic changes and gut microbiota composition. This study investigated the effects of sleep deprivation on pubertal onset and gut microbiota composition in animal models and a human cohort.
Methods
This study comprised 459 boys and 959 girls from the Taiwan Pubertal Longitudinal Study. Sleep duration was evaluated using the self-report Pittsburgh Sleep Quality Index (PSQI) questionnaire. Early sexual maturation was defined by pediatric endocrinologist assessments. Mediation analyses were done to examine the association between sleep parameters, obesity, and early sexual maturation. Besides, Sprague Dawley juvenile rats were exposed to 4 weeks of chronic sleep deprivation. Vaginal opening (VO) and preputial separation (PS) were observed every morning to determine pubertal onset in female and male rats.
Results
The sleep-deprived juvenile rats in the sleep-deprived-female (SDF) and sleep-deprived-male (SDM) groups experienced delayed VO (mean VO days: 33 days in control; 35 days in SDF; p value<0.05) and PS (mean PS days: 42 days in control; 45 days in SDM; p value<0.05), respectively. Relative to their non–sleep-deprived counterparts, the sleep-deprived juvenile rats exhibited lower body weight and body fat percentage. Significant differences in relative bacterial abundance at genus levels and decreased fecal short-chain-fatty-acid levels were identified in both the SDF and SDM groups. In the human cohort, insufficient sleep increased the risk of early sexual maturation, particularly in girls (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09–1.89; p value<0.01). Insufficient sleep also indirectly affected early sexual maturation in girls, with obesity serving as the mediator.
Conclusions
Overall, sleep deprivation altered the timing of puberty in both animal and human models but in different directions. In the rat model, sleep deprivation delayed the pubertal onset in juvenile rats through gut dysbiosis and metabolic changes, leading to a low body weight and body fat percentage. In the human model, sleep deprivation led to fat accumulation, causing obesity in girls, which increased the risk of early puberty.
... As the ovarian follicles mature and start producing estrogens, thelarche develops. However, estrogens exert negative feedback on the hypothalamus and pituitary gland, which is more pronounced on LH than on FSH secretion, leading to a greater delay in the rise of LH compared with FSH (21). Therefore, the rise in FSH secretion can be seen as a "prepuberty", an "introduction" to proper puberty. ...
Introduction
Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as “thelarche variant” (TV), characterized by an FSH-predominant response, although a univocal definition is lacking.
Methods
Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%).
Results
TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm ³ ). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02).
Conclusion
Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a “precocious prepuberty” in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls’ age).
... The mechanisms governing the timing of puberty are currently a rich field of research, but are not completely understood. However, both exogenous and endogenous factors (nutrition, genes, inflammatory status, endocrine disruptor agents, and societal changes) can influence pubertal neuroendocrine events (46). In patients with JIA or other chronic inflammatory conditions, the most frequent pubertal abnormality is delayed puberty, followed by slow clinical progression of puberty, isolated delayed menarche, and decreased duration and intensity of pubertal growth (47,48). ...
Chronic inflammatory conditions, such as juvenile idiopathic arthritis, are associated with growth failure. Growth failure appears to be correlated with both the effects of inflammation and negative effects of glucocorticoids (used as therapeutic option) on the growth hormone axis and locally on the growth plate and bone metabolism. In the last decade, the introduction of biologics has changed the disease course regarding consequences and outcomes. Anyway in some cases, treatment with biologics has failed in restoring normal growth in patients with juvenile idiopathic arthritis; in contrast, several studies have reported improved height velocity and growth rate in patients with juvenile idiopathic arthritis treated with growth hormone. This study aimed to evaluate the impact of growth hormone treatment on the growth and pubertal development in juvenile idiopathic arthritis patients through a narrative review of the literature over the last four decades.
... Subjek merupakan semua anak yang berusia 8 tahun - 17 Mayoritas sampel tergolong memiliki pubertas normal 93,7%, sebanyak 10 sampel penelitian ditemukan mengalami gangguan pubertas (6,2%). Pada sampel yang mengalami gangguan pubertas didapatkan 4 sampel pubertas prekoks dan 6 sampel pubertas terlambat. ...
Background: Puberty is a transition period between childhood and adulthood influenced by various complex factors. Nutrition is one of the most important factors affecting pubertal development. Overweight or obese children are more likely to enter puberty earlier. Severe primary or secondary malnutrition can also delay the onset and progression of puberty. This study aims to determine the relationship between nutritional status and pubertal disorders in Denpasar city orphanage children. Methods: This study was conducted using an analytic research design with a cross-sectional design to determine the relationship between nutritional status and pubertal disorders in Denpasar city orphanage children. This study involved all children in Denpasar city orphanages, Bali, between November and December 2022. Subjects who met the inclusion and exclusion criteria were included in the study. Data were analyzed using SPSS version 25.0 for Windows. Results: This study involved 160 adolescents who had reached the age of puberty in an orphanage in Denpasar City. The sample was classified as having normal puberty, 93.75%, and as many as 10 research samples were found to have puberty disorders (6.25%). The samples were classified as well-nourished (75.00%) and malnutrition (25.00%). This study shows that nutritional status has a significant relationship with pubertal disorders, with a p-value of 0.003 and a prevalence ratio of 7.00 and CI95% (1.90-25.79). Conclusion: This study found that there is a significant relationship between nutritional status and the occurrence of puberty disorders. Adolescents with malnutrition nutritional status have a seven times greater risk of experiencing puberty disorders compared to adolescents with good nutritional status. Latar Belakang: Pubertas merupakan masa transisi antara masa anak-anak dengan dewasa yang di pengeruhi oleh berbagai faktor kompleks. Nutrisi merupakan salah satu faktor terpenting yang mempengaruhi perkembangan pubertas. Anak yang kelebihan berat badan atau obesitas lebih cenderung memasuki masa pubertas lebih awal. Malnutrisi primer atau sekunder yang parah juga dapat menunda permulaan dan perkembangan pubertas. Penelitian ini bertujuan untuk mengetahui hubungan antara status nutrisi dengan gangguan pubertas pada anak panti asuhan kota Denpasar. Metode: Penelitian ini dilakukan menggunakan rancangan penelitian analitik dengan desain potong lintang untuk mengetahui hubungan antara status nutrisi dengan gangguan pubertas pada anak panti asuhan kota Denpasar. Penelitian ini melibatkan semua anak pada panti asuhan kota Denpasar, Bali, diantara periode penelitian November hingga Desember 2022. Subjek yang memenuhi kriteria inklusi dan eksklusi dimasukkan ke dalam penelitian. Hasil: Penelitian ini melibatkan 160 remaja yang telah mencapai usia pubertas di Panti Asuhan yang terletak di Kota Denpasar. Sampel tergolong memiliki pubertas normal 93,75%, sebanyak 10 sampel penelitian ditemukan mengalami gangguan pubertas (6,25%). Sampel tergolong memiliki gizi baik (75,00%) dan malnutrisi (25,00%). Penelitian ini menunjukkan status nutrisi memiliki hubungan signifikan dengan gangguan pubertas dengan nilai p sebesar 0,003 dan prevalence ratio sebesar 7,00 dan IK95% (1,90-25,79). Simpulan: Penelitian ini menemukan bahwa terdapat hubungan yang signifikan antara status nutrisi dengan terjadinya gangguan pubertas. Remaja dengan status nutrisi malnutrisi memiliki risiko tujuh kali lebih besar untuk mengalami gangguan pubertas dibandingkan dengan remaja dengan status nutrisi baik.
... Furthermore, changes in the central nervous system are well documented. 29,30 These rapid changes during maturation likely influence swimming performance in young girls as the anthropometric characteristics of a swimmer affect individual performance. Previous investigations have suggested that limb length, body fat, and frontal surface area are important factors in swimming; for example, elite swimmers tend to have longer arms, a larger hand surface, and lower body fat compared with the normal population, which positively contribute to better sprint swimming performance. ...
Purpose:
The present study aimed to establish differences in load-velocity profiling, active drag (AD), and drag coefficient (Cd) between 3 age groups of female swimmers.
Methods:
Thirty-three swimmers (11, 13, or 16 y old) were recruited. The individual load-velocity profile was determined for the 4 competitive swimming strokes. The maximal velocity (V0), maximal load (L0), L0 normalized to the body mass, AD, and Cd were compared between the groups. A 2-way analysis of variance and correlation analysis were conducted.
Results:
Compared with their younger counterparts, 16-year-old swimmers generally had larger V0, L0, and AD, which was particularly evident when comparing them with 11-year-old swimmers (P ≤ .052). The exception was breaststroke, where no differences were observed in L0 and AD and Cd was smaller in the 16-year-old group than the 11-year-old group (P = .03). There was a negative correlation between Cd and V0 for all groups in backstroke (P ≤ .038) and for the 11-year-old group and 13-year-old group in breaststroke (P ≤ .022) and front crawl (P ≤ .010). For the 16-year-old group, large correlations with V0 were observed for L0, L0 normalized to the body mass, and AD (P ≤ .010) in breaststroke and for L0 and AD with V0 in front crawl (P ≤ .042). In butterfly, large negative correlations with V0 were observed in the 13-year-old group for all parameters (P ≤ .027).
Conclusions:
Greater propulsive force is likely the factor that differentiates the oldest age group from the younger groups, except for breaststroke, where a lower Cd (implying a better technique) is evident in the oldest group.
... Data on puberty stage was categorized into three groups according to Tanner stages (breast and genital development) and age of menarche: (1) early puberty defined as B2 before the age of 8 or menarche before the age of 10 in girls and G2 or testicular volume of ≥ 4 ml before the age of 9 in boys, (2) normal puberty defined as B2 between 9 and 13 years old and age of menarche between 10 and 14 in girls and G2 or testicular volume of ≥ 4 ml between 9 and 13 years old in boys, and (3) late puberty defined as B1 in girls at the age of 13 years or older, age of menarche at the age of 15 or older, and G1 or testicular volume of ≤ 4 ml in boys at the age of 14 years or older [15,16]. Girls under the age of 8 and boys under the age of 9 without signs of puberty were classified as prepubertal and not included in the association analysis of bone health with onset of puberty. ...
Angelman syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD), or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are observed frequently in our clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS. In this prospective cohort study, we describe bone health in 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the bone health index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication use, mobility, body mass index (BMI), and onset of puberty. Children with AS had a mean BHI of −1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (−2.24 SDS) versus non-deletion (−1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (−2.60 vs −1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes.
Conclusions : Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age.
What is Known: • Children with neurological disorders often have a low bone health and higher risk of fractures. • Little is known about bone health in children with Angelman syndrome (AS).
What is New: • Children with AS showed a reduced bone health and this was significantly associated with having a deletion, not being able to walk independently, and late onset of puberty. • Longitudinal analysis showed a significant decrease in bone health as children got older.
... Objective information about onset of puberty was not published before, except from general comments about normal timing of puberty in reviews [37,38]. The mean age at menarche in our cohort was within the normal range, but it was relatively early compared to the mean age of 12-13 years in neurotypical children [39][40][41]. In boys, 10% showed a late onset of puberty. ...
Angelman Syndrome (AS) is a rare genetic disorder caused by lack of maternal UBE3A protein due to a deletion of the chromosome 15q11.2-q13 region, uniparental paternal disomy, imprinting center defect, or pathogenic variant in the UBE3A gene. Characteristics are developmental delay, epilepsy, behavioral, and sleep problems. There is some evidence for hyperphagia, shorter stature, and higher BMI compared to neurotypical children, but longitudinal studies on growth are lacking. In this study, we analyzed prospectively collected data of 145 children with AS, who visited the ENCORE Expertise Center between 2010 and 2021, with a total of 853 visits. Children showed an elevated mean score of 25 on the Dykens Hyperphagia questionnaire (range 11–55) without genotype association. Higher scores were significantly associated with higher body mass index (BMI) standard deviation scores (SDS) (p = 0.004). Mean height was −1.2 SDS (SD 1.3), mean BMI-SDS was 0.6 (SD 1.7); 43% had a BMI-SDS > 1 and 20% had a BMI-SDS > 2. Higher BMI-SDS was significantly associated with non-deletion genotype (p = 0.037) and walking independently (p = 0.023). Height SDS decreased significantly with age (p < 0.001) and BMI-SDS increased significantly with age (p < 0.001. Onset of puberty was normal. In conclusion, children with AS showed moderate hyperphagia, lower height SDS, and higher BMI-SDS compared to norm data, with increasing deviation from the norm with age. It is uncertain how loss of maternal UBE3A function may influence growth. Attention to diet, exercise, and hyperphagia from an early age is recommended to prevent obesity and associated health problems.
... 46e48 Fibroids are dependent on progesterone and estrogen for growth, 49 and during adolescence there are rapidly increasing estrogen and progesterone levels. 50,51 Fibroid onset may correlate with active or chronic inflammation, 52 and inflammation coupled with high estrogen and progesterone levels could create a microenvironment conducive to fibrinogenesis. 53 Although this research cannot establish a causal relationship between genital talc use, douching, and the occurrence of fibroids, the accumulating evidence that these intimate care practices may have negative health effects could provide clinicians with further information for discouraging their use. ...
Background:
Genital talc and douching are practices that can involve exposure to chemical compounds linked to certain gynecologic cancers. However, it is unclear if they are associated with fibroid risk or age at fibroid diagnosis among women.
Objective:
We evaluated the impact of early adolescence genital talc use and douching on prevalent fibroids diagnosed before age 35 and age 50 years among Black/African American and Non-Hispanic White women.
Study design:
Data were from the Sister Study (2003-2020), a prospective cohort of 50,884 U.S. women ages 35-74 years at enrollment. Participants were asked if they ever had a fibroid diagnosis and at what age, and if they used genital talc and/or douched between ages 10-13 years or in the past 12 months. After applying predefined exclusion criteria, our analytic sample size was n=46,316 (Black n=4310, NHW n=42,006). Multivariable logistic regression was used to compute adjusted odds ratio (aOR) and 95% confidence intervals (CI) for having vs. not having early onset fibroids diagnosed before age 35 among women 35-74 years old at enrollment, and fibroids diagnosed before age 50 among women 50-74 years old at enrollment. We adjusted for early life factors (in utero diethylstilbestrol exposure, singleton, or multiple birth, fed soy formular during infancy), and childhood socioeconomic status, relative weight and height compared to peers at age 10. We used multiple imputation (<10% missing in all analyses). Results were stratified by race/ethnicity given that Black women are more likely to develop fibroids at a younger age than NHW women.
Results:
Among Black/African American women, 29% had fibroids diagnosed before age 35. Both genital talc use at age 10-13 (aOR=1.23, CI: 1.06-1.41) and douching (aOR=1.19, 95% CI: 0.95-1.48) were associated with higher odds of having a fibroid diagnosed before age 35. Douching without talc use was not associated with increased odds, but combined use of both genital talc and douche was associated with 52% increased odds of fibroids (CI: 1.14-2.01). Among non-Hispanic White women, 9% reported fibroids diagnosed before age 35. Genital talc use (1.31; 1.20-1.44), but not douching (0.96; 0.77-1.20) at ages 10-13 years was associated with having a fibroid diagnosed before age 35. We observed similar patterns for non-Hispanic White women when we considered fibroids diagnosed before age 50, but neither practice was associated with fibroids diagnosed before age 50 in Black women.
Conclusion:
Genital talc use in early adolescence and combined use with douching, but not douching alone, is associated with prevalent fibroids diagnosed before age 35 among Black/African American women and before ages 35 and 50 among non-Hispanic White women. Early adolescence may be a window of susceptibility for fibroid development, suggesting adolescent girls should be educated on abstention from or alternatives to talc and douching.
... Turk Arch Pediatr 2023, [epub ahead of print] cases of constitutional early puberty (CEP); this situation can be considered the opposite of constitutional delayed growth and puberty. 7 In a study based on the annual follow-up of 170 Israeli (60 girls) and 335 Polish (162 girls) children aged 8-18 years, it was shown that children who were in the higher height percentile (positive "height gap") compared to their pre-puberty target heights had earlier puberty and these children subsequently "physiological catch down" to their target height percentiles. 8 Similarly, according to other studies from Denmark and Israel, the growth pattern at 6-12 months and 5-7 years of age affects the onset and pace of puberty, and tall girls enter puberty earlier and short girls later. ...
... Even though the order of changes in puberty is well established, their timing can be highly variable. For instance, in females, the changes in puberty occur at an average age of 12 years, ranging between 9 and 14 years, in males, the average age of pubertal onset is 12 years and ranges from 10 to 14 years, and usually it is 2 years earlier in girls than boys (Wood et al., 2019). The changes during puberty in girls are marked by a growth spurt rst, followed by breast tissue and menarche development. ...
Preventable diseases in Latin America related to the triple burden of malnutrition in children -undernutrition, hidden hunger, and overweight- are the leading risk factors for premature death, physical and mental disabilities. Moreover, its impacts on health in the following years of life will be negative if they are not treated promptly. There is a need to create health standards and national reference values in Mexico to integrate monitoring, screening, and actions that promote child well-being and development. One of the most used risk-evaluating indicators, the body mass index, does not consider body composition, neglecting relevant information such as possible excess adipose tissue, underestimating the risk of early metabolic alterations, making it more difficult to achieve international health goals. New non-invasive and accessible anthropometric indicators such as the waist-to-height ratio could narrow the gap to improve population health due to its association with cardiovascular risk factors. For this reason, it is crucial to establish its usefulness for nutritional screening and assessment and even to rethink public policies to monitor children’s health status.KeywordsSchoolchildrenAnthropometric assessmentBody mass indexWaist-to-height ratioNutritional status
... Even though the order of changes in puberty is well established, their timing can be highly variable. For instance, in females, the changes in puberty occur at an average age of 12 years, ranging between 9 and 14 years, in males, the average age of pubertal onset is 12 years and ranges from 10 to 14 years, and usually it is 2 years earlier in girls than boys (Wood et al., 2019). The changes during puberty in girls are marked by a growth spurt first, followed by breast tissue and menarche development. ...
Performance of elite athletes depends on a complex combination of determinants ranging from physical, physiological, and morphological characteristics to biomechanics and kinematics inherent to each sport. Among adolescent athletes, growth, maturation, and development significantly influence such attributes. Frequently, young athletes of the same chronological age (CA) exhibit significantly different biological maturation (BM). Influence of BM on physical fitness and performance has been described in previous studies. The individual variations of BM lead to a phenomenon called Relative Age Effect (RAE) that is particularly associated with performance and success both in the competitions as well as in the identification of young talents. In most countries, federated sport at young ages is organized by age groups according to the CA of athletes. Therefore, monitoring athletes’ morphological, physical, and maturity characteristics are important not only to establish a well-timed talent identification system but also to implement adequate training programs, based on those characteristics. Recently, experts have focused their efforts on the attempt to deal with particular differences in BM amongst youth sports, labelling this strategy as “bio-banding” and aiming to band young athletes within a specific CA range based on maturity status.
... Data on puberty stage was categorized into three groups according to Tanner stages (breast and genital development) and age of menarche: 1) early puberty de ned as B2 before the age of 8 or menarche before the age of 10 in girls and G2 or testicular volume of ≥ 4 ml before the age of 9 in boys, 2) normal puberty de ned as B2 between 9-13 years old and age of menarche between 10-14 in girls and G2 or testicular volume of ≥ 4 ml between 9-13 years old in boys and 3) late puberty de ned as B1 in girls at the age of 13 years or older, age of menarche at the age of 15 or older and G1 or testicular volume of ≤ 4 ml in boys at the age of 14 years or older [14,15]. Girls under the age of 8 and boys under the age of 9 without signs of puberty were classi ed as prepubertal and not included in the association analysis of bone health with onset of puberty. ...
Purpose
Angelman Syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD) or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are reported frequently in clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS.
Methods
Prospective cohort study of 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the Bone Health Index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication (ASM) use, mobility, BMI, and onset of puberty.
Results
Children with AS had a mean BHI of -1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (-2.24 SDS) versus non-deletion (-1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (-2.60 vs -1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes.
Conclusions
Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age.
... Growth hormones, including thyroid hormones, testosterone, and estrogen, are commonly involved in the development of bones during the younger age period 28 . Sex hormones are involved in the closure of epiphyseal plates and the halting of longitudinal bone growth at puberty 29 . ...
In plant-derived compounds, phytoestrogens are biologically active substances that exhibit various estrogenic and antiestrogenic effects. With the increasing prevalence of osteoporosis among older women caused by estrogen deficiency, identifying natural substances that can potentially treat the disease is of utmost significance. This review study aimed to explore how phytoestrogen metabolites mimic mammalian estrogens and prevent bone loss following menopause. Phytoestrogens derived from plants have gained considerable attention due to their similarity to mammalian estrogens and lower impact on sensitive tissues, such as the uterus and breasts. One well-established approach to simulate postmenopausal conditions is by using ovariectomized rats or mice (OVX). The administration of phytoestrogens in the OVX murine model has inhibited osteoclast differentiation, activation, and Pyridinoline secretion. Furthermore, these compounds have been shown to enhance bone formation and increase bone mineral density and the expression levels of various osteoblast markers, such as alkaline phosphatase, osteocalcin, osteopontin, and alpha-1 collagen. Several natural phytoestrogen compounds in plants possess a chemical structure akin to 17 beta-estradiol, a steroid hormone. In postmenopausal women with osteoporosis, isoflavones, a type of phytoestrogen, can potentially treat the disease by binding to estrogen receptors on the surface of target cells. Mechanistic investigations have demonstrated that phytoestrogens can retard bone resorption and promote bone formation. Novel approaches in phytoestrogen research could involve investigating the synergistic effects of combining different phytoestrogen compounds, exploring their interactions with other signaling pathways, or assessing their effects on various bone types. Furthermore, identifying novel sources of phytoestrogens could lead to the discovery of new compounds with potent osteoprotective effects.
... Features of adrenarche include increases in body hair, skin changes, and changes in body odor (Auchaus & Rainey, 2004). Although puberty is typically conceptualized as occurring during early adolescence, normative DHEA increases can be detected as early as age 6 (Wood et al., 2019). Concurrent to adrenarche, surges of testosterone and estradiol facilitate the development of secondary sex characteristics, such as breast/gonad development, voice changes, and changes in body shape (Grumbach & Styne, 2003); these changes are known as gonadarche. ...
... Puberty is a complex and dynamic process that is initiated by activation of the hypothalamic-pituitary-gonadal (HPG) axis, with the pulsatile release of pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH) (Wood et al., 2019). In boys, FSH and LH stimulate maturation of the testes (Spaziani et al., 2021), with the earliest reliable physical indicator of pubertal onset being TV enlargement to >3 mL (Koskenniemi et al., 2017). ...
Background:
Epidemiological studies have reported associations of anti-androgenic phthalate metabolite concentrations with later onset of male puberty, but few have assessed associations with progression.
Objectives:
We examined the association of prepubertal urinary phthalate metabolite concentrations with trajectories of pubertal progression among Russian boys.
Methods:
At enrollment (ages 8-9 years), medical history, dietary, and demographic information were collected. At entry and annually to age 19 years, physical examinations including testicular volume (TV) were performed and spot urines collected. Each boy's prepubertal urine samples were pooled, and 15 phthalate metabolites were quantified by isotope dilution LC-MS/MS at Moscow State University. Metabolites of anti-androgenic parent phthalates were included: butylbenzyl (BBzP), di-n-butyl (DnBP), diisobutyl (DiBP), di(2-ethylhexyl) (DEHP) and diisononyl (DiNP) phthalates. We calculated the molar sums of DEHP, DiNP, and all AAP metabolites. We used group-based trajectory models (GBTMs) to identify subgroups of boys who followed similar pubertal trajectories from ages 8-19 years based on annual TV. We used multinomial and ordinal regression models to evaluate whether prepubertal log-transformed phthalate metabolite concentrations were associated with slower or faster pubertal progression trajectories, adjusting for covariates.
Results:
304 boys contributed a total of 752 prepubertal urine samples (median 2, range: 1-6) for creation of individual pools. The median length of follow-up was 10.0 years; 79% of boys were followed beyond age 15. We identified three pubertal progression groups: slower (34%), moderate (43%), and faster (23%) progression. A standard deviation increase in urinary log-monobenzyl phthalate (MBzP) concentrations was associated with higher adjusted odds of being in the slow versus faster pubertal progression trajectory (aOR 1.47, 95% CI 1.06-2.04). None of the other phthalate metabolites were associated with pubertal progression.
Conclusions:
On average, boys with higher concentrations of prepubertal urinary MBzP had a slower tempo of pubertal progression, perhaps attributable to the disruption of androgen-dependent biological pathways.
... And also the exposure to blue light at night is a stress factor and induces oxidative processes in tissues (4)(5)(6). Puberty is a phase of tremendous hormonal, behavioral, and physical changes which a child acquires reproductive function (7). The age of puberty is shifting, and there are rising worries about earlier puberty due to an increased risk of obesity, depression, and psychological issues (8). ...
Purpose
Our study aimed to examine the effects of blue light exposure on prepubertal male rats’ puberty and testis tissue.
Methods
Eighteen 21-day-old male Sprague Dawley rats were divided into three groups consisting of six rats in each group: Control Group (CG), Blue Light-6 hours (BL-6), and Blue Light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The rats of BL-6 and BL-12 were exposed to blue light (450-470nm/irradiance level 0.03uW/cm2) for 6 hours and 12 hours, respectively. Rats were exposed to blue light until the first signs of puberty. The ELISA method was used to analyze the serum levels of FSH, LH, testosterone, DHEA-S, leptin, ghrelin, melatonin, glutathione, glutathione peroxidase, and malondialdehyde. Testes were dissected for histomorphological examination.
Results
The medians of the pubertal entry days of the CG, BL-6, and BL-12 were 38 th , 30 th , and 28 th days, respectively. (p:0.001) The FSH, LH, and testosterone concentrations of all groups were similar. The FSH concentration increased as the LH concentration increased (r: 0.82 p: 0.001). The serum LH concentration increased as serum testosterone, and DHEAS decreased, respectively (r: -0.561, p: 0.01) (r:-0.55 p:0.01). Testicular lengths and weights of the BL groups were smaller compared to CG (p: 0.03),(p: 0.04). GPx was higher for BL-6 and BL-12 than the CG (p:0.021, p:0.024). Testis tissue was compatible with the pubertal period in all groups. As the blue light exposure time increased, spermatogenesis was suppressed, and capillary dilatation and edema in the testis tissue increased.
Conclusion
Our study is the first to show the effects of blue light exposure on male rats’ puberty process. And we showed that exposure to blue light and the duration of exposure lead to precocious puberty in male rats. The blue light exposure suppressed spermatogenesis, marked vasodilatation in the interstitial area of the testis, and disrupted the integrity of the basement membrane. These findings intensified with increasing exposure time.
... Surgical pathology was not stained for Pit-1 because of unavailability of stain; therefore, production of GH by the adenoma cannot be definitively ruled out. However, elevated IGF-1 levels were considered appropriate for the patient's pubertal status and therefore likely resulted from stimulation of GH release by testosterone and estrogen, similar to that which occurs during normal puberty [7]. ...
An 8-year, 7-month-old male presented with puberty symptoms, including a 1.5-year history of facial hair with 9 months of phallic growth, body odor, and acne. Physical examination revealed phallic enlargement but only 4 mL testes bilaterally. Laboratory evaluation revealed markedly elevated LH and testosterone, but a prepubertal FSH level and minimally elevated adrenal androgens. A magnetic resonance imaging scan of the head revealed an anterior pituitary adenoma, and after the patient failed to respond to leuprolide, he was initiated on spironolactone and anastrozole to minimize pubertal progression before transsphenoidal adenomectomy. Postoperatively, the patient had rapid reduction of LH and testosterone, with subsequent cessation of pubertal progression, confirming the diagnosis of an LH-secreting pituitary adenoma despite negative immunoreactivity for LH and FSH. Functioning gonadotroph adenomas are rare and have been documented only in small case series and case reports. When active, these most commonly secrete FSH or co-secrete FSH and LH, and only very rarely result in precocious puberty. Here, we describe a rare case of an isolated LH-secreting functioning gonadotroph adenoma resulting in precocious puberty. This case reinforces the need to critically analyze departures from the typical pubertal sequence and to expand one's differential to include etiologies that can cause unbalanced secretion of gonadotropins.
... In this study, 30% of participants underwent puberty during the study period. This is relevant as the function of the immune system peaks during puberty (37). We have previously reported a lack of sex related differences in immune markers in a younger Ugandan cohort (38) (Kamari paper) and hypothesized that our findings were likely secondary to the prepubertal stage of the participants. ...
Introduction
Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda.
Methods
A prospective observational cohort study was performed in 2017-2021 in Uganda. All participants were between 10-18 years of age and without active co-infections. PHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized LDL, markers of gut integrity and fungal translocation. Groups were compared using Wilcoxon rank sum tests. Changes from baseline were examined with 97.5% confidence intervals on relative fold change. P values were adjusted for false discovery rate.
Results
We enrolled 101 PHIV and 96 HIV-; among these, 89 PHIV and 79 HIV- also had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 yrs (11,15), and 52% were females. In PHIV, median CD4+ cell counts were 988 cells/µL (638, 1308), ART duration was 10 yrs (8, 11), and 85% had viral load <50 copies/mL throughout the study, 53% of participants had a regimen switch between visits, 85% of whom switched to 3TC, TDF and DTG. Over 96 weeks, while hsCRP decreased by 40% in PHIV (p=0.12), I-FABP and BDG both increased by 19 and 38% respectively (p=0.08 and ≤0.01) and did not change in HIV- (p≥0.33). At baseline, PHIVs had higher monocyte activation (sCD14) (p=0.01) and elevated frequencies of non-classical monocytes (p<0.01) compared to HIV- which remained stable over time in PHIV but increased by 34% and 80% respectively in HIV-. At both time points, PHIVs had higher T cell activation (p ≤ 0.03: CD4+/CD8+ T cells expressing HLA-DR and CD38). Only in PHIV, at both timepoints, oxidized LDL was inversely associated with activated T cells(p<0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (β=0.4, 95% CI=0.14,0.57, p<0.01), without changes in other markers.
Conclusion
Ugandan PHIV with viral suppression have some improvement in markers of inflammation over time, however T-cell activation remains elevated. Gut integrity and translocation worsened only in PHIV over time. A deeper understanding of the mechanisms causing immune activation in ART treated African PHIV is crucial.
Zusammenfassung
Patienten mit Diabetes mellitus Typ 1 müssen lebenslang mit Insulin substituiert werden. Dabei wird für jede Einzelne und jeden Einzelnen die passende Insulindosierung gewählt bzw. durch komplexe Algorithmen der AID-Systeme (Automatische Insulindosierung) berechnet. Hierbei fällt auf, dass es immer wieder Kinder und Jugendliche gibt, die einen steigenden Bedarf an Insulin bzw. eine Insulinresistenz aufzeigen. Das Auftreten einer Insulinresistenz bei Kindern und Jugendlichen mit Diabetes mellitus Typ1 – in unserer Publikation definiert als Insulindosierung von über 1U/kg/d – steht augenscheinlich in Zusammenhang mit verschiedenen Einflussgrößen wie u.a. Therapieform und Insulinart, sportlicher Betätigung, Übergewicht, Einnahme einer hormonellen Kontrazeption. Das Ziel der vorliegenden Arbeit ist die Analyse von Daten aus dem DPV-Register. Hierzu wurden die Daten von 48.357 Kindern und Jugendlichen mit T1D herangezogen, um einen Zusammenhang zwischen dem Auftreten einer Insulinresistenz und verschiedenen Einflussfaktoren nachzuweisen. Die Ergebnisse sollen dazu beitragen, Patienten mit ungewöhnlich hohem Insulinbedarf besser beraten zu können und gegebenenfalls durch entsprechende Therapiemaßnahmen zu versuchen, die Insulinresistenz bei Kindern und Jugendlichen mit T1D zu verringern.
I
Summary
The reproductive toxicity due to exposure to aflatoxins was investigated in adult male rats. The present study aims to document the harmful effects of exposure to aflatoxin-B1 in the pre-pubertal stage on the reproductive efficiency of male rats after puberty. The field experiment was extended from 1 November, 2022 to 30 January, 2023.
A total of 80 male rats (35 days old and 75-80 g weight) and 40 mature female rats (75 days old and 155-165 g weight) were included in the current study. Male rats were divided equally to control and treatment groups (AFB1 group). The males were daily administered with distilled water and aflatoxin-B1 (0.3mg/kg/day) per os, respectively. After 15, 25, and 35 days of treatment (pre-puberty, puberty, and post-puberty periods, respectively), ten males from each group were weighted, anesthetized, and sacrificed. Testes, epididymis, seminal vesicles, and prostates were dissected and weighted. Blood samples were collected for assessment the serum concentrations of reproductive hormones (gonadotrophin releasing hormone; GnRH, follicle stimulating hormone; FSH, luteinizing hormone; LH, and testosterone; T). Pituitary and testicular tissue samples were obtained to analyze the expression levels of pituitary GnRHR, FSHβ and LHβ genes and testicular FSHR, LHR, ABP, 3β-HSD, and 17β-HSD genes. Testes and epididymis were obtained for histopathological examination. At puberty (25 days of treatment) and post-puberty (35 days of treatment), tail of epididymis was dissected for semen analysis, including sperm motility, sperm count, sperm viability, and sperm abnormality. The remaining 10 males from each group were matted with experienced females (1 male: 2 females) to find out the fertility index, included pregnancy rate (%), offspring number/dam, duration of pregnancy (day), and weight at birth (g).
Following 15, 25, and 35 days of exposure, the AFB1 treated group revealed decline in the relative weight of testes, epididymis, seminal vesicle, and prostate than control, early at pre-pubertal stage, which continued at pubertal and post-pubertal stages. Compared to control, treated males showed a decrease in serum concentration of GnRH, FSH, LH, and testosterone, and the expression level of pituitary GNRHR, FSHβ, and LHβ genes and testicular LHR, FSHR, ABP, 3β-HSD, and 17β-HSD genes, in all experimental periods. Histological sections of the testicles of treated males showed atrophy of some seminiferous tubules, empty lumen, and massive vacuolization and exfoliation of the germ cells. The histological results of the
II
epididymis showed obliteration of the lumen, necrosis of the epithelial layer, deformed cavities, a climbing epithelial layer, and epithelium hyperplasia compared to the control group. Sperm motility, sperm count, and sperm viability were significantly decreased, while sperm abnormality was significantly increased in the AFB1 group, at puberty and post-puberty. Females matted with AFB1 treated males revealed significant decrease of pregnancy rate, number of offspring, and litter weight at birth in comparison with those matted with control males.
In conclusion, altogether, the current results showed that exposure to aflatoxin-B1 at the pre-pubertal stage have adverse effects on reproduction represented by reduced reproductive efficiency and performance with impaired spermatogenesis after puberty.
The current study uses a mixed method design to investigate Kenyan and Ghanaian adolescents' experiences of puberty, and the relations between gender, country of origin, pubertal status, and body image appraisals ( N = 86; Ghana = 46, Kenya = 40, 52.9% female aged 13 and 14). Qualitative results revealed seven major themes; puberty means a universal period of growth and transition into adulthood but also evokes negative emotions of shame, anxiety, and embarrassment, being in sync with peers during puberty is important and knowing that others in their lives similarly experience puberty is reassuring. Quantitative results revealed significant gender and country differences in pubertal status and body image. Ghanaian adolescents had more advanced pubertal status and more positive body image appraisals compared to Kenyan adolescents. Moderation analysis results revealed that for the Kenyan sample, post‐pubertal males had less favorable body image appraisals than their counterparts who were still pre pubertal whilst for females, post‐pubertal girls had more favorable body images than their counterparts. No such effects were observed with the Ghanaian sample. The findings highlight the need for context considerations in understanding body image during the pubertal transition to help identify relevant protective factors for possible interventions. The results affirm the importance of positive body image promotions for adolescents within the African context and suggest the need for much more comprehensive sex education with gender‐specific components to help allay fears about puberty, thus preventing the development of possible adaptation problems.
Background
Testicular volume is a marker of male pubertal development. Various clinical conditions and their treatments may influence testicular growth.
Objectives
To create ruler‐based age‐dependent pubertal testicular volume references that enable calculation of standard deviation (SD) scores.
Materials and Methods
Study cohort comprised 65 boys who attended clinical examination twice a year from the age of 8.5 years until the attainment of final testicular size. Forty‐nine (75.4%) boys completed the follow‐up and 16 (24.6%) boys dropped out before the attainment of final post‐pubertal testicular size. At each follow‐up visit testicular size was measured with a ruler, orchidometer, and ultrasonography. LMS or LMSP method served as the technique for creating reference growth curves for testicular volumes. Using the novel references for ruler measurements, development of SD scores was assessed in a cohort of boys with unilateral cryptorchidism.
Results
Reference growth curves were constructed separately for ruler, orchidometer, and ultrasonography measurements. Median orchidometer volume of 4 mL, marker of male pubertal onset, occurred at the age of 11.7 years, whereas +2SD curve surpassed 4 mL at 10.2 years and −2SD curve at 13.7 years. Modeled ages at the attainment of 4 mL testicular volume based on ruler measurements were 9.7 years for +2SD curve, 11.5 years for median curve, and 13.6 years for −2SD curve. Ultrasonography‐based volume of 1.3 mL corresponded with the median modeled orchidometer‐based volume of 4 mL. In boys with unilateral cryptorchidism, ruler‐based SD scores decreased during puberty in undescended testes, but not in descended testes.
Discussion and Conclusion
The present study provides reference values for pubertal testicular volume measured with a ruler enabling an age‐dependent assessment of testicular size. Comparison with measurements by an orchidometer and ultrasonography is also presented.
Purpose
Females with above‐average anterior knee laxity values are at increased risk of anterior cruciate ligament (ACL) injury. The purpose of this study was to examine the effects of menarche age (MA) and menarche offset on anterior knee laxity in young, physically active women.
Methods
Anterior knee laxity (KT‐2000) and menstrual characteristics (per self‐report) were recorded in 686 Slovenian sportswomen from team handball, volleyball and basketball club sports (average years sport participation: 7.3 ± 3.6 years). Females were stratified into four groups based on their self‐reported age at menarche: 9–11, 12, 13 and 14+ years. Anterior knee laxity was compared across MA groups using a univariate analysis of variance (ANOVA) with Bonferroni correction, with and without controlling for factors that could potentially differ between groups and influence anterior knee laxity. Females were then stratified into four groups based on the number of years they were away from their age at onset of menarche. Groups were compared using a univariate ANOVA with Bonferroni correction, with and without controlling for factors that differed between groups and could influence anterior knee laxity.
Results
Anterior knee laxity was greater in females who attained menarche at 12 years of age (6.4 ± 1.5 mm) or younger (6.6 ± 1.6 mm) compared to 14 years of age or older (5.8 ± 1.2 mm) ( p < 0.001; partial η ² = 0.032). Anterior knee laxity was 0.7–1.4 mm greater in females who were 5 or more years away from menarche compared to those who were within 2 years of menarche (5.8 ± 1.3 mm; p < 0.001).
Conclusion
Anterior knee laxity is greater in females who attained menarche at a younger age and in females who are 5 or more years postmenarche. Age of menarche represents a critical pubertal event that is easy for women to recall and may provide important insights into factors that moderate anterior knee laxity, a risk factor for ACL injury in women.
Level of Evidence
Level IV.
Aims
Cardiac adaptations in elite, male adolescent youth soccer players have been demonstrated in relation to training status. The time course of these adaptations and the delineation of the influence of volatile growth phases from the training effect on these adaptations remain unclear. Consequently, the aims of the study were to evaluate the impact of 3 years of elite‐level soccer training on changes in left ventricular (LV) structure and function in a group of highly trained elite youth male soccer players (SP) as they transitioned through the pre‐to‐adolescent phase of their growth.
Methods
Twenty‐two male youth SP from the highest Level of English Premier League Academy U‐12 teams were evaluated once a year for three soccer seasons as the players progressed from the U‐12 to U‐14 teams. Fifteen recreationally active control participants (CON) were also evaluated over the same 3‐year period. Two‐dimensional transthoracic echocardiography was used to quantify LV structure and function.
Results
After adjusting for the influence of growth and maturation, training‐induced increases in Years 2 and 3 were noted for: LV end diastolic volume (LVEDV; p = 0.02) and LV end systolic volume (LVESV; p = 0.02) in the SP compared to CON. Training‐induced decrements were noted for LV ejection fraction (LVEF; p = 0.006) and TDI‐S′ (p < 0.001).
Conclusions
An increase in training volume (Years 2 and 3) were aligned with LV volumetric adaptations and decrements in systolic function in the SP that were independent from the influence of rapid somatic growth. Decrements in systolic function were suggestive of a functional reserve for exercise.
Objective : to study the deep and skin temperatures of the knee joint by microwave radiothermometry (RTM) in healthy girls of comparable age in the pre- and pubertal periods. Materials and methods : the study was carried out in the "Problem Scientific Laboratory of Physical Methods of Diagnosis and Treatment" of Rostov State Medical University and the children's health camp "Mir" (Krasny Desant village, Rostov region). It was 45 girls aged 12 years, taking into account gender development, divided into two groups: 1st gr. (n=28) — prepubertal period; 2nd gr. (n =17) — puberty. RTM of the knee joints was performed according to a certain scheme using the MWR2020 system (ex RTM-01-RES) (Moscow, Great Britain). Results : in the groups, the color fields of deep and skin temperature, when compared, are characterized by a slight geometric and color transformation are similar to each other; the lowest temperature is noted in the projection of the patella. Temperature fields of thermoasymmetry make it possible to reveal temperature differences in groups of subjects. In the 2-nd group, there are also higher growth and weight indicators, lower deep and skin temperature in almost all areas of the knee joint, fluctuations reach 0.4 –1.4 ° C. Conclusion : a decrease in temperature in the knee joints in pubertal girls with a relatively mature menstrual cycle reflects general changes in hormonal regulation in this period of development. When forming the temperature indicators of healthy girls, it is necessary to take into account the hormonal processes of puberty with division into groups of pre- and pubertal periods of development.
Context:
Pseudohypoparathyroidism type IA (PHPIA) is a rare genetic disorder characterized by hormone resistance and a typical phenotype named Albright hereditary osteodystrophy. Unawareness of this rare disease leads to delays in diagnosis.
Objectives:
The aims of this study were to describe the clinical and molecular characteristics of patients with genetically confirmed GNAS mutations and to evaluate their long-term outcomes.
Design:
A retrospective search for all patients diagnosed with PHPIA in two referral centers in Israel was conducted.
Results:
Nine children (eight females) belonging to six families were included in the study. Five patients had GNAS missense mutations, two had deletions and two had frameshift mutations. Four mutations were novel. Patients were referred at a mean age of 2.4 years due to congenital hypothyroidism (5 patients), short stature (2 patients), or obesity (2 patients), with a follow-up duration of up to 20 years. Early obesity was observed in the majority of patients. Elevated PTH was documented at a mean age of 3 years, however, hypocalcemia became evident at a mean age of 5.9 years, about 3 years later. All subjects were diagnosed with mild to moderate mental retardation. Female adult height was very short (mean, -2.5 standard deviation) and five females had primary or secondary amenorrhea.
Conclusions:
Long-term follow-up of newborns with a combination of congenital hypothyroidism, early onset obesity, and minor dysmorphic features associated with PHPIA is warranted and molecular analysis is recommended since the complete clinical phenotype may develop a long time after initial presentation.
The gut microbiota was initially thought to develop into a stable, adult-like profile during early postnatal life. The formation of the gut microbiota during early life has been shown to contribute to healthy growth and has lifelong implications for host health. Adolescence, the developmental period between childhood and adulthood, is a critical window for healthy growth and maturation. The composition of the gut microbiota in adolescents is distinct from that of children and adults, which supports the premise that the gut microbiota continues to develop during adolescence toward an adult-like profile. Research has begun to shift its focus from understanding the gut microbiome at the extremes of the lifespan to evaluating the importance of the gut microbiome during adolescence and the role it plays in healthy development. This article provides an overview of adolescent development, host-microbiota interactions, and experimental models used to discern gut microbiota effects on health and disease. The role of the gut microbiota is reviewed as it relates to adolescent: i) brain development, cognition, and behavior; ii) metabolism and adiposity, and iii) skeletal growth and bone mass accrual. Future directions are addressed including omics investigations defining mechanisms through which the gut microbiota influences adolescent development. Further, we discuss advancing non-invasive interventions targeting the adolescent gut microbiota that could be employed to support healthy growth and maturation.
Background
The interplay between pubertal events patterns (PEP) and prostate cancer (PCa) remains poorly understood. Therefore, we investigated the association of PEP with the odds of PCa, and PCa histological differentiation in men residents of Mexico city.
Methods
In this case–control study, we analyzed the information of 371 incident prostate cancer cases and 775 controls matched on age (±5 years). High-grade prostate cancer was classified with Gleason score at diagnosis as ≥8. With information related to beard growth, age at maximum height attainment, and acne severity, the k-medoids algorithm was used to identify three mutually exclusive PEP (early, intermediate, and late). This association was evaluated using multivariable nonconditional logistic regression models.
Results
Men with late PEP, characterized by age at maximum height attainment at around 23 years and no history of acne, was inversely associated with incident (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.15–0.48, p trend <0.01) and high-grade prostate cancer (OR: 0.24; 95% CI: 0.09–0.59, p trend <0.01). Similar associations were observed even after adjusting by IGF-1 (OR: 0.19; 95% CI: 0.06–0.58) and androgens excretion (OR: 0.21; 95% CI: 0.06–0.66). Only the association between the absence of acne and prostate cancer remained significant after adjustment by these biomarkers.
Conclusions
This study suggests that pubertal characteristics might be helpful in identifying risk groups, among which, secondary prevention strategies could be applied. Also, the results agree with previous work suggesting other potential biological mechanisms involved in the etiology of prostate cancer such as the infectious and inflammatory pathways.
The definition of male hypogonadism, used in adult endocrinology, is not fully applicable to paediatrics. A clear understanding of the developmental physiology of the hypothalamic-pituitary-testicular axis is essential for the comprehension of the pathogenesis of hypogonadal states in boys and for the establishment of adequate definitions and classifications in paediatric ages. This is particularly true for central hypogonadism, usually called hypogonadotropic in adults. Because childhood is a period characterised by a physiological state of low gonadotropin and testosterone production, these markers of hypogonadism, typically used in adult endocrinology, are uninformative in the child. This review is focused on the physiological importance of prepubertal Sertoli cell markers – anti-Müllerian hormone (AMH) and inhibin B – and of the intratesticular actions of follicle-stimulating hormone (FSH) and testosterone during early infancy and the first stages of pubertal development. We discuss the role of FSH in regulating the proliferation of Sertoli cells – the main determinant of prepubertal testicular volume – and the secretion of AMH and inhibin B. We also address how intratesticular testosterone concentrations have different effects on the seminiferous tubule function in early infancy and during pubertal development.
Humans are one of the few species undergoing an adolescent growth spurt. Because children enter the spurt at different ages making age a poor maturity measure, longitudinal studies are necessary to identify the growth patterns and identify commonalities in adolescent growth. The standard maturity determinant, peak height velocity (PHV) timing, is difficult to estimate in individuals due to diurnal, postural, and measurement variation. Using prospective longitudinal populations of healthy children from two North American populations, we compared the timing of the adolescent growth spurt’s peak height velocity to normalized heights and hand skeletal maturity radiographs. We found that in healthy children, the adolescent growth spurt is standardized at 90% of final height with similar patterns for children of both sexes beginning at the initiation of the growth spurt. Once children enter the growth spurt, their growth pattern is consistent between children with peak growth at 90% of final height and skeletal maturity closely reflecting growth remaining. This ability to use 90% of final height as easily identified important maturity standard with its close relationship to skeletal maturity represents a significant advance allowing accurate prediction of future growth for individual children and accurate maturity comparisons for future studies of children’s growth.
Background
Dual energy x-ray absorptiometry (DXA) is an established technique for the measurement of body composition. Reference values for these variables, particularly those related to fat mass, are necessary for interpretation and accurate classification of those at risk for obesity-related health complications and in need of lifestyle modifications (diet, physical activity, etc.). Currently, there are no reference values available for GE-Healthcare DXA systems and it is known that whole-body and regional fat mass measures differ by DXA manufacturer.
Objective
To develop reference values by age and sex for DXA-derived fat mass measurements with GE-Healthcare systems.
Methods
A de-identified sample of 3,327 participants (2,076 women, 1,251 men) was obtained from Ball State University’s Clinical Exercise Physiology Laboratory and University of Wisconsin-Milwaukee’s Physical Activity & Health Research Laboratory. All scans were completed using a GE Lunar Prodigy or iDXA and data reported included percent body fat (%BF), fat mass index (FMI), and ratios of android-to-gynoid (A/G), trunk/limb, and trunk/leg fat measurements. Percentiles were calculated and a factorial ANOVA was used to determine differences in the mean values for each variable between age and sex.
Results
Normative reference values for fat mass variables from DXA measurements obtained from GE-Healthcare DXA systems are presented as percentiles for both women and men in 10-year age groups. Women had higher (p<0.01) mean %BF and FMI than men, whereas men had higher (p<0.01) mean ratios of A/G, trunk/limb, and trunk/leg fat measurements than women.
Conclusion
These reference values provide clinicians and researchers with a resource for interpretation of DXA-derived fat mass measurements specific to use with GE-Healthcare DXA systems.
Objective
Early puberty in girls is linked to some adverse outcomes in adolescence and mid-life. We address two research questions: (1) Are socioeconomic circumstances and ethnicity associated with early onset puberty? (2) Are adiposity and/or psychosocial stress associated with observed associations?
Design
Longitudinal data on 5839 girls from the UK Millennium Cohort Study were used to estimate associations between ethnicity, family income, adiposity and psychosocial stress with a marker of puberty.
Main outcome measure
Reported menstruation at age 11 years.
Results
All quoted ORs are statistically significant. Girls in the poorest income quintile were twice as likely (OR=2.1), and the second poorest quintile nearly twice as likely (OR=1.9) to have begun menstruation compared with girls in the richest income quintile. Estimates were roughly halved on adjustment for Body Mass Index and markers of psychosocial stress (poorest, OR=1.5; second poorest, OR=1.5). Indian girls were over 3 times as likely compared with whites to have started menstruation (OR=3.5) and statistical adjustments did not attenuate estimates. The raised odds of menstruation for Pakistani (OR=1.9), Bangladeshi (OR=3.3) and black African (OR=3.0) girls were attenuated to varying extents, from about a third to a half, on adjustment for income and adiposity.
Conclusions
In contemporary UK, excess adiposity and psychosocial stress were associated with social inequalities in early puberty, while material disadvantage and adiposity were linked to ethnic inequalities in early puberty among girls.
Context:
Pediatric obesity has been related to hyperandrogenism and premature adrenarche in previous studies. However, little is known regarding the association between body fat mass and steroidogenic enzyme activities in children.
Objective:
To examine whether body fat mass is associated with serum steroid profiles in girls.
Design, participants, and setting:
We enrolled 242 girls (125 prepubertal, 117 pubertal; aged 7-13 years). Early morning blood samples were drawn at a university hospital to measure serum steroid profiles using gas chromatography-mass spectrometry, and steroidogenic enzyme activities were assessed from the ratios of steroid metabolites.
Main outcome measures:
We evaluated serum steroid profiles and estimated steroidogenic enzyme activities, and their association with anthropometric indices and body composition.
Results:
Prepubertal obese girls demonstrated significantly higher progestin, androgens [dehydroepiandrosterone (DHEA), androstenedione (A-dione), testosterone (T), androsterone], and ratio of steroid metabolites reflecting 17,20 lyase activity [(DHEA + A-dione)/17-hydroxypregnenolone] compared with prepubertal controls. Pubertal obese girls demonstrated significantly higher serum T and androsterone than pubertal controls; however, serum steroid metabolite ratios reflecting steroidogenic enzyme activities did not significantly differ among obese and non-obese girls. Partial correlation analysis revealed that body fat mass was positively correlated with pregnenolone, DHEA, A-dione, T, androsterone, and ratio of [(DHEA + A-dione)/17-hydroxypregnenolone] in prepubertal girls only. Prepubertal girls with increased body fat mass had significantly higher serum DHEA and ratio of [(DHEA + A-dione)/17-hydroxypregnenolone] than controls.
Conclusions:
Increased androgen production in prepubertal obese girls could be at least partly due to increased body fat mass and 17,20-lyase activity.
Millions of the world's children suffer from malnutrition, which predisposes to death from diarrhea and a variety of infectious diseases. Mortality rates among infants and toddlers remain staggeringly high, in part because the pathogenesis of acute malnutrition and its complications remains poorly understood.
We used metabolomic analysis to characterize the metabolic status of Ugandan children with severe acute malnutrition (SAM) and to delineate changes in hormones, metabolites, growth factors, and cytokines during nutritional therapy. We hypothesized that hormonal and metabolic factors measured at presentation would associate with, or predict, subsequent mortality during treatment.
This was a prospective cohort study of 75 severely malnourished children 6 months to 5 years of age treated as inpatients with F-75 and F-100 and supplemental micronutrients; after discharge, they received ready-to-use therapeutic food (RUTF). This increased the mean weight-for-height z-score (WHZ) from -4.27 to -1.75 SD. Blood samples were obtained at presentation, after 2 weeks of inpatient therapy, and after 4 to 10 weeks of RUTF. Plasma samples were analyzed by tandem mass spectrometry and microassays.
At presentation there were high levels of nonesterified fatty acids (NEFA), ketones, and even-chain acylcarnitines, indicating active lipolysis and fatty acid oxidation. In contrast, albumin, amino acids, and C3 carnitine, a by-product of branched-chain amino acids, were low. Levels of insulin, insulin-like growth factor 1 (IGF-1), adiponectin, and leptin were low, while levels of ghrelin, growth hormone, cortisol, interleukin 6 (IL-6), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1) were high. The metabolic and hormonal changes were reversed by formula feeding and RUTF. Biomarkers associated with mortality included HIV, WHZ, and mid-upper-arm circumference (MUAC); the biochemical factor associated most strongly with mortality was low leptin, a marker of adipose reserve and modulator of immune function.
Low leptin predicts mortality in edematous and nonedematous-patients with SAM. Leptin assays might be used to identify malnourished children at highest risk for death.
The complex networks of nutritional, cellular, paracrine, and endocrine factors are closely related with pubertal growth and epiphyseal fusion. Important influencing factors include chondrocyte differentiation capacity, multiple molecular pathways active in the growth plate, and growth hormone-insulin-like growth factor-I axis activation and epiphyseal fusion through estrogen and its receptors. However, the exact mechanisms of these phenomena are still unclear. A better understanding of the detailed processes involved in the pubertal growth spurt and growth plate closure in longitudinal bone growth will help us develop methods to efficiently promote pubertal growth and delay epiphyseal fusion with fewer adverse effects.
Context:
Higher infant growth rates are associated with an increased risk of obesity in later life.
Objective:
We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood.
Design, setting, and participants:
We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months.
Main outcome measures:
Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4).
Results:
We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05).
Conclusions:
Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.
The hypothalamic–pituitary–gonadal (HPG) axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular Leydig and Sertoli cells, respectively, to promote steroidogenesis and spermatogenesis. Both Leydig and Sertoli cells exhibit negative feedback to the pituitary and/or hypothalamus via their products testosterone and inhibin B, respectively, thereby allowing tight regulation of the HPG axis. In particular, LH exerts both acute control on Leydig cells by influencing steroidogenic enzyme activity, as well as chronic control by impacting on Leydig cell differentiation and gene expression. Insulin-like peptide 3 (INSL3) represents an additional and different endpoint of the HPG axis. This Leydig cell hormone interacts with specific receptors, called RXFP2, on Leydig cells themselves to modulate steroidogenesis, and on male germ cells, probably to synergize with androgen-dependent Sertoli cell products to support spermatogenesis. Unlike testosterone, INSL3 is not acutely regulated by the HPG axis, but is a constitutive product of Leydig cells, which reflects their number and/or differentiation status and their ability therefore to produce various factors including steroids, together this is referred to as Leydig cell functional capacity. Because INSL3 is not subject to the acute episodic fluctuations inherent in the HPG axis itself, it serves as an excellent marker for Leydig cell differentiation and functional capacity, as in puberty, or in monitoring the treatment of hypogonadal patients, and at the same time buffering the HPG output.
We aimed to describe the functional changes of Sertoli cells, based on the measurement of serum anti-Müllerian hormone (AMH) and inhibin B during treatment with GnRHa and after its withdrawal in boys with central precocious puberty. Six boys aged 0.8 to 5.5 yr were included. AMH was low at diagnosis in patients >1 yr but within the normal range in younger patients. AMH increased to normal prepubertal levels during treatment. After GnRHa withdrawal, AMH declined concomitantly with the rise in serum testosterone. At diagnosis, inhibin B was elevated and decreased throughout therapy, remaining in the upper normal prepubertal range. In patients with testicular volume above 4 mL AMH remained higher in spite of suppressed FSH. After treatment withdrawal, inhibin B rose towards normal pubertal levels. In conclusion, AMH did not decrease in patients <1 yr reflecting the lack of androgen receptor expression in Sertoli cells in early infancy. Serum inhibin B might result from the contribution of two sources: the mass of Sertoli cells and the stimulation exerted by FSH. Sertoli cell markers might provide additional tools for the diagnosis and treatment followup of boys with central precocious puberty.
Thyroid function is known to play an important role in fetal neurological development, but its role in regulating fetal growth is not well established. Overt maternal and fetal thyroid disorders are associated with reduced birth weight. We hypothesized that, even in the absence of overt thyroid dysfunction, maternal and fetal thyroid function influence fetal growth.
In normal, healthy pregnancies, we aimed to assess whether fetal thyroid hormone at birth (as measured in cord blood) is associated with fetal growth. We also aimed to study whether fetal thyroid hormone at birth is associated with maternal thyroid hormone in the third trimester.
In 616 healthy mother-child pairs, TSH, free T(4) (FT4), and free T(3) (FT3) were measured in mothers at 28 wk gestation and in umbilical cord blood at birth. Birth weight, length, head circumference, and tricep and bicep skinfold thicknesses were measured on the babies.
Cord FT4 was associated with birth weight (r = 0.25; P < 0.001), length (r = 0.17; P < 0.001), and sum of skinfolds (r = 0.19; P < 0.001). There were no associations between birth measurements and either cord TSH or cord FT3. Maternal FT4 and cord FT4 were correlated (r = 0.14; P = 0.0004), and there were weaker negative associations between maternal TSH and cord FT4 (r = -0.08; P = 0.04) and FT3 (r = -0.10; P = 0.01).
Associations between cord FT4 and birth size suggest that fetal thyroid function may be important in regulating fetal growth, both of skeletal size and fat. The correlation between third-trimester maternal FT4 and cord FT4 supports the belief that maternal T(4) crosses the placenta even in late gestation.
Anti-Müllerian hormone (AMH), which is secreted by immature Sertoli cells, triggers the involution of the fetal Müllerian ducts. AMH is a testis-specific marker used for diagnosis in infants with ambiguous genitalia or bilateral cryptorchidism.
The aim of the study was to describe the ontogeny of AMH secretion through life in healthy males.
This was a population-based study of healthy volunteers. Participants: Participants included 1027 healthy males from birth (cord blood) to 69 yr. A subgroup was followed up longitudinally through the infantile minipuberty [(in cord blood, and at 3 and 12 months), n=55] and another group through puberty [(biannual measurements), n=83].
Serum AMH was determined by a sensitive immunoassay. Serum testosterone, LH, and FSH were measured, and pubertal staging was performed in boys aged 6 to 20 yr (n=616).
Serum AMH was above the detection limit in all samples with a marked variation according to age and pubertal status. The median AMH level in cord blood was 148 pmol/liter and increased significantly to the highest observed levels at 3 months (P<0.0001). AMH declined at 12 months (P<0.0001) and remained at a relatively stable level throughout childhood until puberty, when AMH declined progressively with adults exhibiting 3-4% of infant levels.
Based on this extensive data set, we found detectable AMH serum levels at all ages, with the highest measured levels during infancy. At the time of puberty, AMH concentrations declined and remained relatively stable throughout adulthood. The potential physiological role of AMH and clinical applicability of AMH measurements remain to be determined.
To examine the role of androgens on birth weight in genetic models of altered androgen signalling.
Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH).
(1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH.
Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references.
Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6).
CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.
Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established.
A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships.
The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide.
345 probands, 18 family members, and 292 controls were studied.
Reproductive phenotypes throughout reproductive life and before and after therapy were examined.
Rare sequence variants in TAC3/TACR3 were detected.
In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism.
Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time.
Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR–/–), Stat5ab–/–, and GHR–/– mice treated with IGF-I. Reduced bone growth in GHR–/– mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR–/– mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR–/– on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab–/– mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR–/– mice, indicating that the effects of GH in bone may not involve Stat5 activation.
Adult rats (16-18/group) received a single intratesticular injection of 25, 100 or 400 microliters glycerol solution (7:3 in distilled water, v/v). Half of the rats in each group were given implants of testosterone, a testosterone-filled Silastic capsule (1.5 cm length) to provide serum values of testosterone within the normal range. After 1 week all animals were killed by decapitation. Serum concentrations of gonadotrophins, testosterone and immunoactive inhibin as well as testicular concentrations of testosterone and bioactive inhibin were determined. Testicular histology was studied in Paraplast-embedded tissue stained with PAS and haematoxylin-eosin. Glycerol treatment caused a dose-dependent ablation of spermatogenesis in a distinct area around the site of injection. Serum concentrations of FSH increased proportionally with increasing spermatogenic damage while serum LH and testosterone remained unaltered except with the highest glycerol dose. The rise in serum FSH was significantly correlated with serum (r = -0.70, P less than 0.001) and testicular (r = -0.66, P less than 0.001) concentrations of inhibin. A less pronounced correlation was found between LH and serum inhibin (r = 0.48). No correlation was found between the concentrations of LH and testicular inhibin or between serum concentrations of FSH and serum testosterone in the 25 and 100 microliters groups. Maintenance of low to normal serum testosterone concentrations by means of Silastic implants blocked the elevation of FSH in glycerol-treated animals but failed to affect significantly serum FSH in untreated rats. In all testosterone treated rats testicular inhibin concentrations were markedly reduced in the presence of lowered concentrations (7-14%) of testicular testosterone and unaltered serum FSH concentrations.
CONTEXT
The early activation of the hypothalamic-pituitary-gonadal axis during infancy can be used in the evaluation of infants suspected of disorders of sex development (DSD). However, few data exists on sex-specific reference ranges for these hormones during early life.
OBJECTIVE
To evaluate sex-differences in reproductive hormone concentrations in serum from healthy infants in order to define sex-specific cut-off values and to apply these in infants with DSD.
DESIGN
A cross-sectional study.
SETTING
A tertiary center for pediatric endocrinology at the University Hospital of Copenhagen.
PATIENTS OR OTHER PARTICIPANTS
1,840 healthy infants and 27 DSD patients aged 2-5 months.
MAIN OUTCOME MEASURES
Serum concentrations of LH, FSH, testosterone, estradiol, SHBG, inhibin B, AMH, DHEA, DHEAS, 17-OHP, androstenedione, and LH/FSH-ratio.
RESULTS
LH and FSH concentrations showed overlap between sexes with LH being highest in boys and FSH being highest in girls. The LH/FSH-ratio separated infant boys from girls with minimal overlap at a cut-off value of 0.32. Inhibin B and AMH concentrations were markedly higher in boys compared to girls, with minimal or no overlap, respectively. In infants with Klinefelter syndrome, 45,X/46,XY mosaicism and male phenotype, and Turner syndrome, respectively, the LH/FSH-ratio matched the gender-of-rearing. However, infants with complete androgen insensitivity syndrome had LH/FSH-ratios within male range.
CONCLUSIONS
Reference ranges for reproductive hormones and LH/FSH-ratio during mini-puberty were established in this study. The classifiers that best separated sex in mini-puberty were AMH, LH/FSH-ratio and testosterone. Use of the LH/FSH-ratio may add valuable information in the work-up of infants suspected of DSD.
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.
Objective:
Many studies that examine growth in growth-restricted children at birth do not discriminate between fetal growth restriction (FGR) and small for gestational age (SGA). These terms however are not synonymous. In SGA, stunting and increased weight gain have been reported. We do not know if this holds true for FGR. Our aim was to study postnatal growth until age 12.5?years in a cohort of children born FGR due to early onset placental insufficiency, and its relation to FGR severity.
Design:
Prospective cohort study, follow-up of an antenatal randomised controlled trial in two tertiary centres.
Patients:
Children aged 12.5?years born after FGR, with mothers who had severe early onset hypertensive pregnancy disorders (N=96).
Main outcome measures:
Anthropometry at age 12.5?years in SD scores (SDS).
Results:
Mean height SDS (SD) corrected for target height was -0.09 (0.94), mean body mass index (BMI) SDS was 0.00 (1.16) and mean head circumference SDS was -0.37 (1.11). Catch-up growth was at fastest rate between term age and 3?months and similar for height (0.55 SDS/months) and weight (0.49 SDS/months). Neither FGR severity nor gestational age was related to height and BMI at age 12.5?years.
Conclusions:
Children born growth restricted due to early onset placental insufficiency have height and BMI scores comparable to their age-matched peers at age 12.5?years. FGR severity was not related to height and BMI at age 12.5?years. These reassuring results differ from most studies that examine SGA children.
Study objective:
To investigate the potential of serum anti-Müllerian hormone (AMH) and inhibin B (INHB) levels as markers for pubertal progression rate in girls with central precocious puberty (CPP). DESIGN, SETTING, AND PARTICIPANTS, INTERWENTIONS, AND MAIN OUTCOME MEASURES: A total of 148 girls were enrolled, including 65 girls with premature thelarche (PT) and 83 girls with CPP, grouped based on the results of Gonadotropin-releasing hormone (GnRH) stimulation tests. Girls with CPP underwent a six-month follow-up, and were further divided into two subgroups: progressive CPP (P-CPP) group (n=55) and slowly progressive CPP (SP-CPP) group (n=28). Serum AMH and INHB levels were assessed in all enrolled girls. Using receiver operating characteristic (ROC) curves, we analysed the diagnostic performance of AMH and INHB to differentiate the 2 forms of CPP.
Results:
Our data showed that AMH and INHB offer the potential to act as markers that distinguish SP-CPP from P-CPP. Compared with SP-CPP group, girls with P-CPP showed lower AMH levels and higher INHB levels. Based on the receiver operating characteristics (ROC) analysis, the area under the curve (AUC) was 0.92 for the combination of AMH and INHB, with 80% sensitivity and 89.3% specificity.
Conclusion:
Our results suggest that serum AMH and INHB levels provide a promisng method in differentiating SP-CPP from P-CPP.
Objective:
To examine prospectively multiple indicators of pregnancy health and associations with adverse birth outcomes within a large, diverse sample of contemporary women.
Design:
A cohort of pregnant women who gave birth during 2009-10.
Population:
We enrolled a sample of 6822 pregnant New Zealand (NZ) women: 11% of all births in NZ during the recruitment period.
Methods:
We analysed a number of maternal health indicators and behaviours during pregnancy in relation to birth outcomes using multivariable logistic regression. Associations were described using adjusted odds ratios and 95% confidence intervals.
Main outcome measures:
Three birth outcomes, low birth weight (LBW), pre-term birth (PTB) and delivery type, were measured via linkage with maternity hospital perinatal databases. Small for gestational age (SGA) was then defined as below the 10th percentile by week of gestation.
Results:
Modelling of birth outcomes after adjusting for confounders indicated patterns of increased risk of LBW and PTB for women who smoke, have elevated pre-pregnancy body mass index (BMI), or with insufficient pregnancy weight gain. SGA was associated with maternal smoking, alcohol use, insufficient weight gain and nausea and vomiting during pregnancy. Risk of caesarean section was associated with having a diagnosed illness before pregnancy, elevated BMI, greater pregnancy weight gain and less pregnancy exercise. Number of risk factor variables were then used to model birth outcomes. Women with multiple risk factors were at increased risk compared with those who had no risk factors.
Conclusions:
Women with multiple health risks are at particular risk of adverse birth outcomes.
Mean plasma GH concentrations increase in normal boys during mid- to late-puberty. To investigate the nature of the pituitary secretory events and/or altered metabolic clearance responsible for these serum GH concentration changes, we performed multiple-parameter deconvolution analysis of 46 24-h serum GH concentration-time series obtained from normal boys at various stages of puberty and young adulthood. The subjects ranged in chronological age from 7-27 yr. The height and weight of each subject were between the 5th and 95th percentile for age. The calculated daily mass of GH secreted was greatest (P less than 0.001) in late pubertal boys (mean +/- SE, 1810 +/- 250 micrograms/24 h) and was triple the value in prepubertal boys (610 +/- 65 micrograms/24 h). When the values were normalized and expressed as mass of GH secreted per unit (m2) body surface area or per L distribution volume, GH secretion in late pubertal boys was still significantly greater than that in any other group (P less than 0.05). These ...
The timing of puberty is of great interest to health providers and the lay public as well. The age at the onset of puberty has been related to public health issues, e.g., early puberty has been related to metabolic syndrome and various cancers, whereas delayed puberty has been linked to osteoporosis. Pubertal onset is influenced by various factors. Herein, the role on the timing of puberty of genetic and epigenetic, ethnic/racial, and environmental factors, like socioeconomic factors, the place of residence, and endocrine-disrupting chemicals, will be described briefly. In girls, most studies show a decline in the age of menarche and/or the onset of puberty in the twentieth century, although some studies show a leveling off of the secular trend. In recent decades a moderate correlation between the onset of puberty and the age at menarche has been observed. This is considered to be due to the fact that the early-maturing girls present a compensatory delay in pubertal progression. The studies examining the onset of puberty in boys are much fewer. The results of the studies on the secular trend of pubertal onset in boys are inconsistent, others showing a decline in the age of puberty, whereas a number of studies show no change in pubertal onset whatsoever. The data on spermarche (ejacularche) are very limited, thus preventing the estimation of its secular trend.
The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis.
To assess the accuracy of inhibin B and the gonadotropin releasing hormone agonist test for the diagnosis of hypogonadotropic hypogonadism (HH).
We performed a retrospective analysis of data collected 2009-2014 using a strict clinical protocol. All prepubertal nonunderweight girls, aged 13-17.5 years with Tanner breast stage B1/B2 and low estradiol levels, were tested and re-examined at 6-month intervals (n = 21). Constitutional delay of growth and puberty was defined by spontaneous menarche; HH was identified by association with specific causes of HH or no spontaneous progress of puberty during follow-up. Inhibin B was measured using enzyme-linked immunosorbent assay, and follicle-stimulating hormone and luteinizing hormone (basal and stimulated by triptorelin) were measured using a chemiluminescence immunoassay.
The cohort comprised 12 girls with constitutional delay of growth and puberty and 9 girls with HH. The causes of HH included hypopituitarism (n = 3), Prader-Willi syndrome, chromosomal aberration, intellectual disability syndrome with ataxia, and idiopathic causes (n = 2). Each measurement, basal inhibin B <20 pg/mL or stimulated follicle-stimulating hormone (4 hours) <11 IU/L, demonstrated a sensitivity and a specificity of 100% for the detection of HH. Stimulated luteinizing hormone (4 hours) <9 IU/L showed 100% sensitivity but only 83% specificity.
Inhibin B seems to be the ideal measurement for detecting HH in girls. The gonadotropin releasing hormone agonist test is an alternative diagnostic modality, although this approach is more invasive and laborious.
Copyright © 2015 Elsevier Inc. All rights reserved.
Objective:
The distinction between constitutional delay of growth and puberty (CDGP) and isolated hypogonadotropic hypogonadism (IHH) in males with delayed puberty is difficult but important for timely treatment. We assessed the accuracy of the GnRH agonist test (triptorelin 0·1 mg) in comparison with inhibin B alone or in combination with basal LH for the diagnosis of IHH.
Patients and measurements:
Ninety-seven prepubertal males aged 13·7-17·5 year, with testicular volumes ≤4 ml, were examined every 6 months. CDGP was defined by a testicular volume ≥8 ml after 18 months, and IHH was defined by a testicular volume <5 ml after 24 months follow-up. Inhibin B concentrations were measured by ELISA, and LH concentrations were measured by CLIA.
Results:
At follow-up, the cohort comprised 52 boys with CDGP and nine with IHH. The other patients were lost for follow-up (n = 10), had not reached follow-up yet (n = 20) or did not reach a definite testicular volume (n = 6). Basal LH <0·3 IU/l, stimulated LH (4 h) <5·3 IU/l or inhibin B <111 pg/ml had 100% sensitivity for IHH. Only LH (4 h) <5·3 IU/l had a specificity of 100%, and the specificities of basal LH <0·3 IU/l (88%) or inhibin B <110 pg/ml (92%) were lower. The combination of LH <0·3 IU/l with inhibin B <111 pg/ml increased the specificity to 98·1%.
Conclusions:
The LH response 4 h after GnRH agonist stimulation has an excellent accuracy for the diagnosis of IHH in prepubertal boys with delayed puberty. However, the measurement of inhibin B and basal LH in combination is a valid, reliable and less-invasive alternative test.
Background:
Accurate and selective assessment of testosterone requires use of a sensitive LC-MS/MS method, especially at low levels as those seen in young children.
Methods:
The present longitudinal study of 20 healthy children from the Copenhagen Puberty Study followed every 6 months for 5 years evaluates the longitudinal increase in serum testosterone before, during and after pubertal onset quantified by a newly developed LC-MS/MS method in comparison with immunoassay. Testosterone concentrations in serum samples (n = 177) were determined by LC-MS/MS (detection limit 0.1 nmol/l) and by immunoassay (detection limit 0.23 nmol/l).
Results:
Serum concentrations of testosterone increased gradually with age by both methods. However, serum testosterone was quantifiable in 9/10 girls prior to pubic hair development measured with LC-MS/MS, and in 2/10 girls measured with immunoassay. In boys, testosterone was quantifiable in 10/10 boys 1 year prior to pubic hair development measured with LC-MS/MS, and only in 1/10 boys measured with immunoassay. Serum testosterone levels were quantifiable 1.5 years (range 0.5-2.5) earlier using LC-MS/MS.
Conclusion:
Assessment of longitudinal circulating levels of serum testosterone using a selective LC-MS/MS method proved to be more sensitive in predicting early peripubertal changes in healthy children compared to levels determined by immunoassay.
Context:
Studies of hormone changes in the peripubertal period note increases in adrenal hormones prior to increases in sex steroids. It is unclear how these processes are related to each other, except through this temporal relationship.
Objective:
Examine relationships in adrenal and sex hormones in 252 peripubertal girls.
Setting and design:
Longitudinal observation study. School districts, at the Cincinnati site of the Breast Cancer and the Environment Research Centers, between 2004-2010. Participants were recruited between ages 6 and 7 years of age and were seen every 6 months. Main outcome measures included height, weight, maturation status, and fasting blood specimen. Serum was analyzed for selected hormones every six months, beginning 30 months prior to, and extending to 6 months after, breast development. Androstenedione, estradiol, estrone, and T were measured by high-performance liquid chromatography (HPLC) with tandem mass spectrometry. Dehydroepiandrosterone-sulfate (DHEA-S) and SHBG also were measured.
Results:
DHEA-S concentrations increased 24 months before breast development; androstenedione and estrone between 12 to 18 months before breast development; whereas estradiol and T increased, and SHBG fell between 6 and 12 months before breast development. Girls with greater body mass index had lower estradiol concentrations at onset of breast development as well as 6 months after pubertal onset.
Conclusions:
Serum estrone and DHEA-S increased prior to estradiol concentrations, and the increase in estradiol occurred prior to breast development. Heavier peripubertal girls have lower estradiol levels at puberty, suggesting peripheral conversion of adrenal androgens to estrone.
Whether or not adolescence should be treated as a special period, there is now no doubt that the brain changes much during adolescence. From an evolutionary perspective, the idea of an under developed brain which is not fit for purpose until adulthood is illogical. Rather, the adolescent brain is likely to support the challenges specific to that period of life. New imaging techniques show striking changes in white and grey matter between 11 and 25 years of age, with increased connectivity between brain regions, and increased dopaminergic activity in the pre-frontal cortices, striatum and limbic system and the pathways linking them. The brain is dynamic, with some areas developing faster and becoming more dominant until other areas catch up. Plausible mechanisms link these changes to cognitive and behavioural features of adolescence. The changing brain may lead to abrupt behavioural change with attendant risks, but such a brain is flexible and can respond quickly and imaginatively. Society allows adolescent exuberance and creativity to be bounded and explored in relative safety. In healthcare settings these changes are especially relevant to young people with long term conditions as they move to young adult life; such young people need to learn to manage their health conditions with the support of their healthcare providers.
Human growth is a complex process starting at conception and completing in adolescence at the time of growth plate fusion. Growth can be divided into four phases: (1) fetal, where the predominant endocrine factors controlling growth are insulin and the insulin-like growth factors. (2) Infancy, where growth is mainly dependent upon nutrition. (3) Childhood, where the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis and thyroid hormone are most important. (4) Puberty, where along with the GH-IGF-I axis the activation of the hypothalamo-pituitary-gonadal axis to generate sex steroid secretion becomes vital to the completion of growth. GH is released from the pituitary in a pulsatile fashion under the control of GHRH, Ghrelin, and somatostatin and, via a complex signal transduction cascade, initiates the release of IGF-I within many tissues but predominantly the liver and at the growth plate. IGF-I acts in an autocrine and paracrine manner via the IGF-I receptor to stimulate cell proliferation and longitudinal growth. Activation of the pituitary-gonadal axis during puberty occurs via a complex interaction of factors including kisspeptin, leptin, gonadotrophin releasing hormone, and tachykinin ultimately leading to augmentation of GH secretion, the pubertal growth spurt, and fusion of the growth plates. Many other hormones can affect the GH-IGF-I system or directly affect cell proliferation at the growth plate including thyroid hormone, vitamin D, and corticosteroids. © 2013 Wiley Periodicals, Inc.
Of the many factors that regulate linear growth, IGF-I has a central role in epiphyseal chondrocyte development. Whether IGF-I is solely of systemic or also of local origin is uncertain, as is how other growth factors interact with IGF-I at the growth plate. We studied the proliferative effects of IGF-I on juvenile bovine epiphyseal chondrocytes fractionated by density gradient centrifugation. Cell density correlated with size, glycogen content, and gene expression patterns. There was a gradient of response to IGF-I, with the greatest proliferative response in high-density cells corresponding to the reserve zone, as measured by [3H]thymidine uptake. Low-density (hypertrophic zone) cells proliferated only when exposed to IGF-I and basic fibroblast growth factor (FGF). The gradient of IGF-I response correlated with [125I]IGF-I binding as determined by Scatchard analysis: IGF-I receptor number was 10-fold greater in reserve zone cells than in hypertrophic cells. When exposed to basic FGF for 24 hours, IGF-I binding in hypertrophic cells increased 3-fold. In contrast, no specific binding of GH was demonstrated in juvenile bovine chondrocytes. GH produced neither signal transducer and activator of transcription phosphorylation, increased proliferation, nor increased IGF-I mRNA levels in any chondrocyte fraction. IGF-I mRNA levels were extremely low at 800-1100 copies/microg 18S RNA in bovine chondrocytes. These results suggest that the major regulator of chondrocyte proliferation is systemic IGF-I; FGFs may influence the actions of IGF-I at the growth plate by altering its receptor number in chondrocytes.
Endochondral ossification is the process that results in both the replacement of the embryonic cartilaginous skeleton during organogenesis and the growth of long bones until adult height is achieved. Chondrocytes play a central role in this process, contributing to longitudinal growth through a combination of proliferation, extracellular matrix (ECM) secretion and hypertrophy. Terminally differentiated hypertrophic chondrocytes then die, allowing the invasion of a mixture of cells that collectively replace the cartilage tissue with bone tissue. The behaviour of growth plate chondrocytes is tightly regulated at all stages of endochondral ossification by a complex network of interactions between circulating hormones (including GH and thyroid hormone), locally produced growth factors (including Indian hedgehog, WNTs, bone morphogenetic proteins and fibroblast growth factors) and the components of the ECM secreted by the chondrocytes (including collagens, proteoglycans, thrombospondins and matrilins). In turn, chondrocytes secrete factors that regulate the behaviour of the invading bone cells, including vascular endothelial growth factor and receptor activator of NFκB ligand. This review discusses how the growth plate chondrocyte contributes to endochondral ossification, with some emphasis on recent advances.
Maternal nutrition during pregnancy has a pivotal role in the regulation of placental-fetal development and thereby affects the lifelong health and productivity of offspring. Suboptimal maternal nutrition yields low birth weight, with substantial effect on the short-term morbidity of the newborn. The placenta is the organ through which gases, nutrients, and wastes are exchanged between the maternal-fetal circulations. The size, morphology, and nutrient transfer capacity of the placenta determine the prenatal growth trajectory of the fetus to influence birth weight. Transplacental exchange depends on uterine, placental, and umbilical blood flow. Most important, maternal nutrition influences factors associated not only with placental homeostasis but also with optimal fetal development. This review associates fetal growth with maternal nutrition during pregnancy, placental growth and vascular development, and placental nutrient transport.
Gynecomastia, defined as benign proliferation of male breast glandular tissue, is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications. Although a fairly common presentation in the primary care setting and mostly of benign etiology, it can cause patients considerable anxiety. The initial step is to rule out pseudogynecomastia by careful history taking and physical examination. A stepwise approach that includes imaging and laboratory testing to exclude neoplasms and endocrinopathies may facilitate cost-effective diagnosis. If results of all studies are normal, idiopathic gynecomastia is diagnosed. The evidence in this area is mainly of observational nature and lower quality.
We tested predictions about psychosocial factors in the onset of menarche using data from a longitudinal study of 16-year-old girls. Belsky, Steinberg, and Draper have proposed a model that seeks to explain individual differences in maturational timing in terms of stressful childhood experiences. Their model hypothesizes that (1) individuals who grow up under conditions of family stress (2) experience behavioral and psychological problems which (3) provoke earlier reproductive readiness. In this study, the effect of family stressors on menarche was mediated by neither behavior problems nor weight, contrary to the predictions. However, the most provocative proposition advanced by Belsky et al. received empirical support. Family conflict and father absence in childhood predicted an earlier age of menarche, and these factors in combination with weight showed some evidence of an additive influence on menarche. A genetic inheritance model may provide a more parsimonious account of these data than does a conditional adaptation model derived from sociobiology.
Karlberg J. (Department of Anatomy, University of Gothenburg, Sweden and the Departments of Pediatrics and Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA). On the construction of the infancy-childhood-puberty growth standard. Acta Paediatr Scand [Suppl] 356: 26, 1989.
Using the infancy-childhood-puberty (ICP) growth model, the postnatal linear growth curve is mathematically broken down into three components: infancy, childhood and puberty. The fact that each component of this model seems to represent a defined biological phase of the growth process, extends its clinical application. The principles used to construct the ICP growth standard and the basic‘clinical’ICP-based growth charts are described. These charts have a number of advantages over the conventional growth charts currently in use. Most importantly, the ICP growth chart provides reference values not only for total growth but also for each of the three individual components. Using this methodology, the magnitude and the onset of each component can be assessed in an individual child. The age at onset of the childhood component, which is a newly discovered and important feature of human growth, can easily be detected in an individual child. Furthermore, prepubertal growth, onset of puberty and pubertal growth can be accurately assessed, because the difference in pubertal maturation is taken into account when setting standards during adolescence. The methodology also offers a new and highly accurate predictor of final height and permits assessment of growth rates over shorter and longer periods using a simple and effective method of assessing change. The ICP growth model appears to be a refined instrument for detecting and understanding growth disturbances.
Environmental influences that impair growth and development in early life may be risk factors for ischaemic heart disease. To test this hypothesis, 5654 men born during 1911-30 were traced. They were born in six districts of Hertfordshire, England, and their weights in infancy were recorded. 92.4% were breast fed. Men with the lowest weights at birth and at one year had the highest death rates from ischaemic heart disease. The standardised mortality ratios fell from 111 in men who weighed 18 pounds (8.2 kg) or less at one year to 42 in those who weighed 27 pounds (12.3 kg) or more. Measures that promote prenatal and postnatal growth may reduce deaths from ischaemic heart disease. Promotion of postnatal growth may be especially important in boys who weigh below 7.5 pounds (3.4 kg) at birth.
Inhibins are proteins consisting of two subunits, 18 K alpha- and 14 K beta-subunits, linked by disulfide bonds. Two forms of inhibins A and B consisting of a common alpha-subunit and a similar but distinguishable beta-subunit specifically suppress the secretion and cell content of FSH in a delayed action. The production of inhibin is regulated mainly by FSH; therefore, a reciprocal relation between FSH and inhibin is established. Each subunit (alpha-, beta A- or beta B-) is encoded by a different mRNA species. Inhibin secreted in response to FSH from the pituitary originates primarily in the granulosa cells of the ovary and the Sertoli cells or testes. Two beta-subunits, beta A beta A, beta A beta B, or beta B beta B form a new molecule, activin, that has opposite endocrine function to inhibin, but in the presence of inhibin, the activity of inhibin overrode that of activin. Follistatin, a single-chain polypeptide with no structurally similarity to inhibin, also specifically inhibits the release of FSH, approximately one third potency of inhibin. This probably is due to the fact that inhibin suppresses both FSH secretion and cell content of FSH whereas follistatin primarily inhibits the release of FSH. In addition to the endocrine function, these gonadal proteins also exert paracrine function on gonadotropin-mediated steroidogenesis. Outside the reproductive system, inhibin and activin also play a role in hemoglobin production, erythroid cell differentiation; all three proteins, together with TGF beta, are involved in immunosuppresion.
Spontaneous pubertal growth was studied in eight patients with the syndrome of androgen insensitivity to obtain information on the growth-promoting action of estrogens. In one additional patient (who had a gonadectomy before puberty), the effect of exogenous estrogens was studied. Mean age at peak height velocity (12.7 years) was closer to that in normal girls than to that in normal boys. Mean peak height velocity (7.4 cm/yr) was as in normal girls (7.3 cm/yr), but was lower than in normal boys (9.3 cm/yr). Bone age corresponded better to male standards. Mean adult height (172.3 cm) was lower than in normal men (-0.6 SD), but higher than in normal women (+1.4 SD). In the patient who had a gonadectomy, estrogen replacement caused a higher peak height velocity (12 cm/yr), but lower adult height (160.5 cm) than in the patients with intact gonads who received no treatments. We conclude that in normal girls, the pubertal growth spurt also results from the action of estrogens rather than of adrenal androgens. To ensure normal pubertal growth, physiologic estrogen replacement in hypogonadal females should be started at a bone age of about 11 years, and should not be delayed in the hope of achieving a greater mature height.
Insulin-like growth factor-1 (IGF-1), a mitogenic polypeptide, is usually considered the sole effector by means of which growth hormone increases tissue mass. However, growth hormone, but not IGF-1, directly promotes the differentiation of cultured preadipocytes to adipocytes. Adipocytes newly differentiated from precursor cells in response to growth hormone were shown to be much more sensitive to the mitogenic effect of IGF-1 than the precursor cells. The result of IGF-1 action is therefore a selective multiplication of young differentiated cells (cloned expansion). This supports the concept of a dual effector system in which the preferred target cells of IGF-1 action are created by the direct action of growth hormone.
Longitudinally-based height and height velocity charts for North American children are presented. Centiles are given for early, middle, and late maturers. The shape of the curves is taken from a review of longitudinal studies, and the prepubertal and adult centiles for height attained are taken from National Center for Health Statistics data. The charts are suitable for following an individual child's progress during observation or treatment throughout the growth period, including puberty.
Growth hormone increases tissue formation by acting both directly and indirectly on target cells. The direct action promotes the differentiation of precursor cells; this has been demonstrated for two mesenchymal cell types. Insulin-like growth factor I (IGF-I) is not able to substitute for growth hormone in promoting this differentiation, but it is proposed that its mitogenic action selectively promotes cell multiplication in young differentiated clones. As tissue growth results from both the creation of new differentiated cells and their subsequent clonal expansion, both effectors increase tissue growth, but by different means.
Bone-specific Greulich-Pyle and Tanner-Whitehouse assessments of skeletal age were made of 2,009 roentgenograms of 62 boys and 82 girls studied semilongitudinally from two to fourteen years. The median G-P 1 skeletal ages were similar to the chronologic ages as were the median G-P 2 skeletal ages. The median Tanner-Whitehouse skeletal ages were markedly greater than the corresponding chronological ages especially from six to nine years in the boys and from four to eight years in the girls.
The regulation of fetal growth is complex and poorly known. During the first trimester of pregnancy, no strict endocrine mechanisms are involved, but embryonic growth might be controlled at the level of the individual organs by supply of nutrients and by locally active growth factors. Later on, fetal growth depends essentially upon the maternoplacental cooperation in delivering nutrients to the fetus. Therefore, the major role of hormones in fetal growth is to mediate the utilization of available substrate. In late gestation, placental size and fetal growth rate are well correlated, pointing to a key role of the placenta in the regulation of fetal growth. It is therefore important to understand the molecular mechanisms involved in regulating placental development and endocrine functions. TGF alpha and EGF might play major roles as suggested by the modulation of their receptors with placental development, and by the specific alterations of EGF receptors in intrauterine growth retardation. In addition, human placenta specifically secretes placental growth hormone, the level of which is significantly decreased in the sera of pregnant women bearing a fetus with intrauterine growth retardation.
Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing.
The patient was tall (204 cm [80.3 in.]) and had incomplete epiphyseal closure, with a history of continued linear growth into adulthood despite otherwise normal pubertal development. He was normally masculinized and had bilateral axillary acanthosis nigricans. Serum estradiol and estrone concentrations were elevated, and serum testosterone concentrations were normal. Serum follicle-stimulating hormone and luteinizing hormone concentrations were increased. Glucose tolerance was impaired, and hyperinsulinemia was present. The bone mineral density of the lumbar spine was 0.745 g per square centimeter, 3.1 SD below the mean for age-matched normal women; there was biochemical evidence of increased bone turnover. The patient had no detectable response to estrogen administration, despite a 10-fold increase in the serum free estradiol concentration. Conformation analysis of his estrogen-receptor gene revealed a variant banding pattern in exon 2. Direct sequencing of exon 2 revealed a cytosine-to-thymine transition at codon 157 of both alleles, resulting in a premature stop codon. The patient's parents were heterozygous carriers of this mutation, and pedigree analysis revealed consanguinity.
Disruption of the estrogen receptor in humans need not be lethal. Estrogen is important for bone maturation and mineralization in men as well as women.
Inhibin B levels were measured in serum from 400 healthy Danish prepubertal, pubertal, and adolescent males, aged 6-20 yr, in a cross-sectional study using a recently developed immunoassay that is specific for inhibin B, the physiologically important inhibin form in men. In addition, serum levels of FSH, LH, testosterone, and estradiol levels were measured. Serum levels of inhibin B, FSH, LH, testosterone, and estradiol all increased significantly between stages I and II of puberty. From stage II of puberty the inhibin B level was relatively constant, whereas the FSH level continued to increase between stages II and III. From stage III of puberty the FSH level was also relatively constant, although there was a nonsignificant trend of slightly decreased FSH levels at pubertal stage V compared to stage IV. The levels of serum LH, testosterone, and estradiol increased progressively throughout puberty. In prepubertal boys younger than 9 yr, there were no correlation between inhibin B and the other three hormones. In prepubertal boys older than 9 yr, a significant positive correlation was observed between inhibin B and FSH, LH, and testosterone. However, at this pubertal stage, each hormone correlated strongly with age, and when the effect of age was taken into account, only the partial correlation between inhibin B and LH/testosterone remained statistically significant. At stage II of puberty, the positive partial correlation between inhibin B and LH/testosterone was still present. At stage III of puberty, an negative partial correlation between inhibin B and FSH, LH, and estradiol was present, whereas no correlation between inhibin B and testosterone could be observed from stage III onward. The negative correlation between inhibin B and FSH persisted from stage III of puberty onward, whereas the correlation between inhibin B and LH and between inhibin B and estradiol was nonsignificant at stages IV and V of puberty. In conclusion, in boys, serum inhibin B levels increase early in puberty; by pubertal stage II the adult level of inhibin B has been reached. The correlation of inhibin B to FSH, LH, and testosterone changes during pubertal development. Early puberty is characterized by a positive correlation between inhibin B and LH/testosterone, but no correlation to FSH. Late puberty (from stage III) is characterized by a negative correlation between inhibin B and FSH (which is maintained in adult men), a diminishing negative correlation between inhibin B and LH, and no correlation between inhibin B and testosterone, suggesting that developmental and maturational processes in the hypothalamic-pituitary-gonadal axis take place, leading to the establishment of the closed loop feedback regulation system operating in adult men. The positive correlation between inhibin B and LH/ testosterone at the time when serum inhibin B levels rise early in puberty suggests that Leydig cell factors may play an important role in the maturation and stimulation of Sertoli cells in the beginning of pubertal development.
The aim of this study was to examine the influence of very low socioeconomic status, physical injury and psychological trauma on the menarchal age of deported girls who lived in besieged Srebrenica, a town that had a highly disrupted environment from the end of 1992 to mid 1995. The Srebrenica girls had a significantly higher mean menarchal age compared with a control group who lived mainly in peaceful communities in the unoccupied territory of Bosnia and Herzegovina.
Conclusion Our results show that psychological trauma, physical injury and low socioeconomic status, which provoked by the events of war, delay the age of menarche.