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Testosterone metabolism. Testosterone is a steroid hormone metabolized from cholesterol by desmolase activity. Pregnenolone is a product of this reaction and is converted to testosterone via intermediates 17-alpha-hydroxypregnelonone, dehydroepiandrosterone and 4-androstene-3, 17-dione (Yamazaki and Shimada 1997). In the alternative pathway, testoster- one is produced with intermediates including pregnenolone, progesterone and 17-alpha-hydroxyprogesterone (Rose et al. 1997). In blood circulation, testosterone binds to sex hormone binding globulin (SHBG) and is, thus, protected from meta- bolic degradation but also biologically inactive. Only a small fraction of the hormone is free and active (able to bind to its receptor or to be further metabolized) (Maruyama et al. 1987). In some target tissues (adipose tissue, brain) aromatase cata- lyzes the conversion of testosterone to the female sex steroid hormone estradiol. The effect is then mediated via estrogen receptors (Carreau et al. 2003). Alternatively, 5α-reductase reduces testosterone to more a potent androgen dihydrotestoster- one (DHT) which also binds androgen receptor (Askew et al. 2007, Roy and Chatterjee 1995, Shidaifat 2009).
Source publication
Testosterone is a steroid sex hormone with an important role in the physiology in both sexes. It is involved in the development of morphological and functional parameters of the body via multiple molecular mechanisms. Intensive research focused on testosterone reveals associations with cognitive abilities and behavior and its causative role in sex...
Context in source publication
Context 1
... together, the goal of this review is to provide the comprehensive overview of testosterone physiolo- gy, cognition, social behavior and brain organization providing some issues for future research. Testosterone is conserved through most vertebrates indicating its importance in evolution and develop- ment (Hau et al. 2000, Cornil et al. 2011, Sharma and Chaturvedi 2011). Testosterone is often considered and called male sex hormone, but in fact, it regulates sex drive and many other processes in both sexes. In men, the main production of testosterone is localized to the smooth endoplasmatic reticulum of Leydig cells in the testicles (Brown-Séquard 1889). Plasma of normal healthy women also contains about ten times lower testosterone concentration than an adult human male body, but females are more sensitive to the hor- mone. Half of testosterone amount in females is gen- erated by the ovaries, the rest by the cortex of supra- renal glands (Lobotsky et al. 1964, Wu et al. 2010). Biosynthesis of testosterone occurs also in other tis- sues, even in some regions of the brain (Mensah- Nyagan et al. 1996, Matsunaga et al. 2002). A simpli- fied scheme of testosterone metabolism is illustrated on Figure 1. This trajectory is essential to be men- tioned, because all these metabolic steps can influ- ence final concentration of testosterone and its effect on target tissues. Molecular mechanism of testosterone action can vary (Fig. 2). Testosterone as well as dihydrotestoster- one are ligands of the nuclear androgen receptor (Askew et al. 2007). In the classical genomic pathway, the ligand activated receptor is an important transcrip- tion factor that regulates expression of genes involved in cell proliferation, differentiation, metabolism and apoptosis (Nelson et al. 2002). For the regulation of expression protein coactivators are recruited (Estebanez-Perpina et al. 2005). Beyond the ...
Citations
... Androgens are key regulators of male sexual differentiation and the development of normal male phenotypes. Testosterone, the major human androgen, plays a dominant role in sexual dimorphism (3). Genetic and environmental effects modulate the gene expression of steroid-metabolising enzymes in the steroidogenic cascade, consistent with the expression regulation of the corresponding receptors, implying a complex mechanism of androgen action. ...
Background
Accumulating evidence suggests that the autism spectrum disorder (ASD) population exhibits altered hormone levels, including androgens. However, studies on the regulation of androgens, such as testosterone and dehydroepiandrosterone (DHEA), in relation to sex differences in individuals with ASD are limited and inconsistent. We conducted the systematic review with meta-analysis to quantitatively summarise the blood, urine, or saliva androgen data between individuals with ASD and controls.
Methods
A systematic search was conducted for eligible studies published before 16 January 2023 in six international and two Chinese databases. We computed summary statistics with a random-effects model. Publication bias was assessed using funnel plots and heterogeneity using I² statistics. Subgroup analysis was performed by age, sex, sample source, and measurement method to explain the heterogeneity.
Results
17 case-control studies (individuals with ASD, 825; controls, 669) were assessed. Androgen levels were significantly higher in individuals with ASD than that in controls (SMD: 0.27, 95% CI: 0.06–0.48, P=0.01). Subgroup analysis showed significantly elevated levels of urinary total testosterone, urinary DHEA, and free testosterone in individuals with ASD. DHEA level was also significantly elevated in males with ASD.
Conclusion
Androgen levels, especially free testosterone, may be elevated in individuals with ASD and DHEA levels may be specifically elevated in males.
... In addition, hyperandrogenemia stands as one of the diagnostic criteria for PCOS and impacts 60-80% of patients [15]. Female are actually more sensitive to testosterone even though it is known as a male hormone [16]. Growing evidences showed that testosterone may play an important role between the serum VD level and the risk of PCOS. ...
Background
Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain.
Objective
We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms.
Methods
We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms.
Results
TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587–0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968–0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process.
Conclusion
Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.
... Testosterone belongs to the group of steroid hormones which is produced in the gonads and adrenal cortex. The serum level of testosterone is ten times higher in male compared to female patients, however, females are more sensitive to testosterone serum level imbalance [17]. This hormone regulates the function of cells by binding to the nuclear androgen receptors, a high density of which occurs in sebaceous glands [18]. ...
Introduction
Acne vulgaris is one of the most common dermatological diseases. Hormonal imbalance affects the skin condition and results in the formation of acne vulgaris lesions.
Aim
To evaluate serum levels of testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), triglycerides (TG), and high-density lipoprotein (HDL) in patients with acne vulgaris and compare them to healthy population.
Material and methods
Forty-one patients with acne vulgaris and 47 age- and body mass index (BMI)-matched controls were enrolled in the study.
Results
The mean ± SD testosterone serum level in the study group was 0.45 ±1.03 ng/ml in females and 4.24 ±0.68 in males and in the control group 0.73 ±2.03 ng/ml and 5.3 ±1.3 ng/ml in females and males, respectively. The prolactin serum level was 16.73 ±8.02 ng/ml in the study group and in the control group 13.74 ±8.71 ng/ml (p = 0.011). The FSH serum level was 12.17 ±16.93 mIU/ml and 6.2 ±7.3 mIU/ml in the study and control groups, respectively (p = 0.0001), whereas LH serum levels were 18.44 ±19.71 mIU/ml and 11.26 ±8 mIU/ml, respectively (p = 0.2659). The HDL serum level was 65.63 ±15.67 mg/dl in the study group and 61.53 ±15.89 mg/dl in the control group (p = 0.219), and TG levels were 175.29 ±82.15 mg/dl and 87.32 ±30.64 mg/dl, respectively (p < 0.00001).
Conclusions
Our study demonstrates, that hormonal and lipid imbalance could be linked to acne vulgaris formation. Evaluation of hormonal and lipid abnormalities could help in treatment decisions and could affect the occurrence of complications and the course of acne.
... Hypogonadism can be confirmed if the patient has symptoms of hypogonadism, a family history of symptoms of hypogonadism, decreased testosterone levels, or if the patient has had an infection, trauma, or medical therapy related to hormonal changes. 7 Hypogonadism is classified into 2, namely primary and secondary. Primary hypogonadism is usually caused by genetic disorders (such as Klinefelter syndrome, X chromosome abnormalities, Sertoli-cell only syndrome), infections such as orchitis, or testicular trauma and other abnormalities of the testicles. ...
Infertility is a failure to get pregnant after one year of sexual intercourse without using contraception. The causes of infertility, especially in men, are very complex, including the aging process, hormonal disorders, lifestyle, environment, metabolic disease, and genetic problems. One of the most difficult causes in male infertility is genetic problems. In this case, a 35 year old man was reported with primary infertility and often experienced premature ejaculation and even anejaculation. Previously, the patient had repeatedly consulted about his condition at other fertility service centers. The conclusion obtained was that the patient had azoospermia with bilateral varicoceles and had been given hormone therapy but had not yet found a final diagnosis so the patient was still confused about what had happened to him. At the first visit the patient underwent a sperm analysis and the results were azoospermia. Then, based on the results of the history and physical examination, which indicated hypogonadism, a Y chromosome microdeletion examination was carried out, and a deletion was found in the AZFc region, which is a marker of infertility that causes spermatogenic failure. The examination was continued with karyotyping, the result was 47.XXY, consistent with the condition of Klinefelter syndrome. Conclusion: Carry out a karyotyping examination if you find signs and symptoms that suggest primary hypogonadism in male infertility. This can be done to streamline the diagnostic approach time in patients with primary hypogonadism, especially those with infertility.
... Some data reported conflicting results and supported a non-consistent effect of androgens (54). Studies on molecular mechanism of androgen action on the brain indicated that testosterone have a direct impact on glial cells thereby can modulate the myelinisation mechanism, synapse, and dendritic branching number as well as neuron growth (55). It has also been shown that even though gonadotropic neurons do not express androgen receptors, testosterone can modulate these neurons through a neuropeptide called kisspeptin which is not only expressed in the hypothalamic-pituitary-gonadal axis (HPG) but also in the limbic regions of the brain implicated in the emotional and cognitive behaviour (Mills et al., 2018. ...
Objective: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. Methods: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. Control group: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. Results: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. Conclusions: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.
... In men, testosterone plays a crucial role in the maintenance of muscular integrity, bone mineral density, and sexual function, with its deficiency potentially result in issues such as infertility, depression, fatigue, and decreased libido [3]. Despite being present at lower levels in women, testosterone exhibits greater sensitivity in females [4]. Emerging evidence suggests that testosterone levels may be correlated with suicidal behavior in females with bipolar disorder, and bioavailable testosterone is associated with the severity of COVID-19 infection in women [5,6]. ...
Objective
Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females.
Methods
Initially, a rigorous quality control process was employed to identify suitable instrumental single nucleotide polymorphisms (SNPs) associated with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined through a two-sample Mendelian randomization. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were applied in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Furthermore, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized to further validate the robustness of the results.
Results
Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1407, 95%CI: 1.0627–1.2244, P = 0.0015) and endometrial cancer (OR = 1.4610, 95%CI: 1.2695–1.6813, P = 1.22E-06). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1764, 95%CI: 1.0846–1.2761, P = 0.0005), cervical cancer(OR = 1.0020, 95%CI: 1.0007–1.0032, P = 0.0077), and endometrial cancer(OR = 1.4124, 95%CI: 1.2083–1.6511, P = 0.0001). Additionally, our results demonstrated a negative causal relationship between BT and ovarian cancer (OR = 0.8649, 95%CI: 0.7750–0.9653, P = 0.0320). However, no causal relationship was found between BT, TT and other types of cancer (corrected P > 0.05).
Conclusions
This study elucidates the role of testosterone on the development of breast cancer, endometrial cancer, ovarian cancer, and cervical cancer. It also hints at a potential but fragile link between testosterone and bladder cancer, as well as thyroid cancer. Nonetheless, it's worth noting that no statistically significant relationship between testosterone and various other types of cancer in females was identified.
... These hormones suppress atrophy and neurodegeneration induced by stress hormones in different brain parts [174][175][176] and induce neuronal plasticity and synaptic remodeling [177]. Moreover, testosterone improves mood and behavior and reforms cognitive skills [178]. Stress exposure downregulates testosterone and estradiol receptors in the hippocampus. ...
... Testosterone is converted to dihydrotestosterone (DHT) and estradiol, acting on androgen and estradiol receptors. Testosterone induces its effect via genomic and non-genomic pathways [178] and exerts anxiolytic and antidepressant effects by these receptors [180][181][182]. The hippocampus seems to be the main region that testosterone affects [179]. ...
Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.
... In men, testosterone plays a crucial role in the maintenance of muscular integrity, bone mineral density, and sexual function, and its de ciency may result in infertility, depression, fatigue, and decreased libido [3]. Despite circulating at lower levels in women, testosterone exhibits greater sensitivity in females [4]. Emerging evidence suggests that testosterone levels may correlate with suicidal behavior in females with bipolar disorder, and bioavailable testosterone is associated with the severity of COVID-19 infection in women [5,6]. ...
Objective: Previous observational studies have explored the correlation between testosterone and cancer risk. However, the causal association between testosterone and various cancer types in women remains inconclusive. The objective of this Mendelian randomization study is to evaluate the causal links between total testosterone (TT) and bioavailable testosterone (BT) with cancer risk in females.
Methods: Initially, a rigorous quality control process was used to identify suitable instrumental single nucleotide polymorphisms (SNPs) linked with the exposure under investigation that exhibited a significant association. The genetic causal relationship between female testosterone levels and the risk of developing cancers was examined via two-sample Mendelian randomization. A variety of analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed in the investigation. Key findings were primarily based on the results obtained via IVW (random effects), and sensitivity analyses were conducted to assess the reliability of the obtained results. Moreover, maximum likelihood, penalized weighted median, and IVW (fixed effects) methods were utilized in order to further validate the robustness of the results.
Results: Based on the results of IVW analysis, our study indicated a positive causal relationship between BT and breast cancer (OR = 1.1184, 95%CI: 1.0448-1.1971, P = 0.0083) and endometrial cancer (OR = 1.4995, 95%CI: 1.3179-1.7061, P = 9.94E-09). Moreover, our findings also showed a positive causal association between TT and breast cancer (OR = 1.1403, 95%CI: 1.0574-1.2298, P = 0.0043), cervical cancer (OR = 1.0017, 95%CI: 1.0006-1.0028, P =0.0122), and endometrial cancer (OR = 1.5046, 95%CI: 1.3103-1.7277, P = 9.06E-08). However, no causal relationship was found with BT and TT on other types of cancer (corrected P> 0.05).
Conclusions: This study elucidates the role of testosterone in the development of breast cancer, endometrial cancer, and cervical cancer, while also indicating a potential tenuous link between testosterone and bladder cancer as well as skin cancer. Nonetheless, no statistically meaningful relationship between testosterone and various other types of cancer in females was observed.
... It is mainly synthesized by the Leydig cells of the testes in males, whereas the ovaries, the adrenal gland, and the placenta produce it in females. Biosynthesis of T also occurs in some regions of the brain (Durdiakova et al., 2011). This hormone is responsible for the development and maintenance of primary and secondary sexual characteristics in males such as the penis, muscles, and beard, through binding to intracellular receptors, modulation of ligandactivated ion channels, and interacting with neurotransmitters. ...
... A4 jest metabolitem pośrednim powstającym na drodze przekształcenia P4 w T [3]. Androgeny produkowane są przez komórki Leydiga jąder, jajniki i warstwę korową nadnerczy, regulując w sposób dymorficzny emocjonalne, motywacyjne oraz kognitywne aspekty zachowań seksualnych [5]. ...
Wraz ze wzrostem średniej długości życia i starzeniem się ludzkiej populacji, zwiększa się odsetek osób cierpiących na choroby neurodegeneracyjne (NDs). W przypadku choroby Alzheimera (AD), choroby Parkinsona (PD) i stwardnienia zanikowego bocznego (ALS), zaobserwowano wyraźną dysproporcję w zachorowalności w zależności od płci. Uważa się, że może to mieć związek z wpływem steroidów płciowych na ryzyko wystąpienia tych chorób. Dane epidemiologiczne pokazują, że na AD częściej cierpią kobiety, natomiast PD i ALS są bardziej rozpowszechnione u mężczyzn. Liczne badania wskazują na neuroprotekcyjne działanie estrogenów i potwierdzają, że czynniki redukujące ich poziom zwiększają ryzyko zachorowania na NDs. Odwrotne efekty zaobserwowano dla androgenów, chociaż dowiedziono także korzystnego wpływu tych hormonów. Zrozumienie potencjalnej roli steroidów płciowych i ich receptorów w patogenezie i przebiegu NDs może przyczynić się do lepszego poznania molekularnych mechanizmów leżących u podłoża tych schorzeń, a tym samym do opracowania skuteczniejszych sposobów prewencji i leczenia.
