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![Gonadotrophs in the anterior pituitary (AP) secrete essential luteinizing hormone (LH; green circle) and follicle-stimulating hormone (FSH; blue circle) to regulate reproduction. The canonical mechanisms regulating gonadotropin secretion in women are as follows: 1) stimulation by GnRH secreted by the hypothalamus [via either a rapid non-genomic (non-transcriptional regulation) pathway (as shown by green, bold, dotted lines), or via a slow genomic (transcriptional regulation) pathway (as shown by green, thin, dotted lines)], and 2) genomic suppression by nuclear-localized estrogen receptors (ERs) (as shown by red, dotted lines) activated by estradiol.](publication/340450486/figure/fig1/AS:877122293886976@1586133659543/Gonadotrophs-in-the-anterior-pituitary-AP-secrete-essential-luteinizing-hormone-LH.png)
Gonadotrophs in the anterior pituitary (AP) secrete essential luteinizing hormone (LH; green circle) and follicle-stimulating hormone (FSH; blue circle) to regulate reproduction. The canonical mechanisms regulating gonadotropin secretion in women are as follows: 1) stimulation by GnRH secreted by the hypothalamus [via either a rapid non-genomic (non-transcriptional regulation) pathway (as shown by green, bold, dotted lines), or via a slow genomic (transcriptional regulation) pathway (as shown by green, thin, dotted lines)], and 2) genomic suppression by nuclear-localized estrogen receptors (ERs) (as shown by red, dotted lines) activated by estradiol.
Source publication
Previous studies in the 1960s and 1970s have reported that both gonadotropin-releasing hormone (GnRH) and estradiol-activated nuclear estrogen receptors regulate gonadotropin secretion in women. However, I had previously reported that gonadotroph function is regulated by complex crosstalk between several membrane receptors. RNA-seq had previously r...
Contexts in source publication
Context 1
... are important cells located in the anterior pituitaries (APs), which secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to regulate reproduction in animals ( Fig. ...
Context 2
... might colocalize with GnRHR in the limited area of the plasma membrane of gonadotrophs. To test this hypothesis, I examined the colocalization of GnRHR with each one of these receptors (and with either the LHβ subunit or FSHβ subunit) in both AP tissue and cultured AP cells using immunofluorescence microscopy [33][34][35]. I found that GPR61 (Fig. 6a), GPR153 (Fig. 6b), and AMHR2 (Fig. 6c) colocalize with GnRHRs in the limited area of the plasma membrane in bovine gonadotrophs. The positive overlap coefficient calculated by confocal data analysis software was very strong (more than 0.70) between GnRHR and GPR61, between GnRHR and GPR153, and between GnRHR and AMHR2 on the cell-surface of gonadotrophs ...
Citations
... Oestrogens mainly comprise oestradiol (E2), oestrone (E1) and oestriol (E3). Under the action of FSH and LH, the ovaries synthesize oestrogen from low-density lipoprotein cholesterol [42]. E2 is the predominant natural oestrogen in females. ...
Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.
... Many reports of reduced reproductive performance in cows fed feed contaminated with mycotoxins, particularly zearalenone. Thus, the leading cause of infertility in cows and heifers are considered to be impaired maturation and ovulation of follicles (Fushimi et al., 2015;Kadokawa, 2020), as well as the formation of ovarian cysts (Abbasian et al., 2018). ...
The article presents data on the distribution and seasonal dynamics of subclinical abortions in cows with mycotoxin poisoning, particularly zearalenone. Subclinical abortion is a common phenomenon among cows in dairy farms and causes significant economic losses due to multiple unsuccessful inseminations, reduced animal productivity, and premature culling. The research aimed to study the seasonal fluctuations of hidden abortions in cows and the influence of the method of keeping in the conditions of feed contamination with microscopic fungi and their toxins. To diagnose hidden abortions, cows were diagnosed with the pregnancy on the 32nd day after insemination. When pregnancy was confirmed, the animals were examined for 92 days. At the same time, if the pregnancy was not confirmed, it was considered that an abortion had occurred. Seasonal fluctuations of subclinical abortions were established - the most significant number (up to 13.6 %) was diagnosed at the end of spring, associated with many animals entering the hunt after the transit period. It is also important that at that time, the number of mycotoxins in feed reached record values, which led to abortions due to toxic effects on the organs of the reproductive system in particular and the body in general. A large number of abortions (11.2 %) in the summer season was also confirmed. At the same time, animals kept free all year received a similar diet containing mycotoxins. At the same time, a concomitant negative factor was temperature shock at this time of year. This whole complex of reasons led to subclinical abortions followed by the resorption of the fetus. Sonographically, areas of reduced echogenicity of the uterus in cows after abortions were detected, which is evidence of the development of subclinical endometritis, confirmed by the uterus's heterogeneous echogenicity. In infertile animals, the presence of follicles with cavities and small yellow bodies that did not extend beyond the surface of the ovary was established sonographically. This indicates a hypofunctional state and impaired folliculogenesis and luteogenesis.
... В той час, коли під дією ароматази вивільняється велика кількість ендогенних естрогеноподібних речовин із кормом корови отримують велику кількість зеараленону, який за хімічною будовою подібний до естрадіолу-17β (екзогенний шлях надходження естрогеноподібних речовин) (Dänicke et al., 2014;Liu & Applegate, 2020;Falkauskas et al., 2023). При цьому знижується інгібуючий вплив зеараленону на релізинг-гормон (Kadokawa, 2020). ...
Mycotoxin zearalenone is a phytoestrogenic substance that can disrupt the functioning of the organs of the reproductive system of cows. At the same time, a hyperestrogenic state occurs, which leads to overeating, multiple unsuccessful inseminations and infertility of cows. The purpose of the research is to investigate the effect of a single application of drugs based on aromatase inhibitors on the main biochemical and hormonal parameters of the blood of cows, as well as to establish their effectiveness during spontaneous expression of desire and when applying synchronization schemes. The effect of a single dose of aromatase inhibitors on the dynamics of sex hormones in cows, which directly affect the formation of the dominant follicle and its ovulation, was investigated. At the same time, a 1.56-fold decrease in estradiol, a 1.67-fold increase in progesterone, a 1.29-fold increase in luteinizing hormone, and a 1.76-fold increase in follicle-stimulating hormone were found. At the same time, the maturation of the dominant follicle and its ovulation at a size of 22 to 24 mm have been established. A change in the biochemical parameters of the blood serum of cows after the use of products based on an aromatase inhibitor was revealed. A tendency was established to restore the level of calcium to 2.01±0.27 mmol/l, phosphorus – 1.1±0.41 mmol/l, magnesium – 0.87±0.11 mmol/l, selenium –1.0± 0.1 mmol/l. At the same time, the level of creatinine decreased by 1.2 times compared to sick animals, the indicators of liver transferases also tended to decrease. A significant decrease in the blood urea index by 1.69 times was established, which indicates the restoration of protein and lipid metabolism. The indicators of fertilization of cows with spontaneous manifestation of sexual desire when using agents based on aromatase inhibitors were studied. At the same time, the fertility rate ranged from 69.39% in cows older than 5 years to 80.39% in cows after the 1st calving. A positive effect of aromatase inhibitors, introduced before the use of estrus synchronization schemes in cows, was established on the development of the dominant follicle, luteogenesis and the appearance of a new wave of follicle development. Fertilization averaged from 68.1% to 76.42%.
... Gonadotrophs in the anterior pituitary (AP) secrete gonadotropins, luteinizing hormone (LH) and folliclestimulating hormone (FSH), to regulate reproductive functions in mammals 1 . These cells are controlled by gonadotropin-releasing hormone (GnRH) via the GnRH receptor on the gonadotroph surface. ...
Brain ethanolamine plasmalogens (EPls) are the only known ligands of G-protein-coupled receptor 61, a novel receptor that stimulates follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), secretion by bovine gonadotrophs. We hypothesized that the recently developed neuroprotective EPls extracted from scallop ( Pecten yessoensis ) (scallop EPls) could stimulate FSH secretion by gonadotrophs. To test this hypothesis, bovine gonadotrophs were cultured for 3.5 days and treated with increasing concentrations of scallop EPls. FSH secretion was stimulated by all tested concentrations of scallop EPls ( P < 0.05). Surprisingly, LH secretion was stimulated by both 0.5 ( P < 0.05) and 5 ( P < 0.01) ng/mL of scallop EPls. To clarify the important differences between bovine brain and scallop EPls, we utilized two-dimensional liquid chromatography–mass spectrometry, which revealed 44 peaks, including 10 large peaks. Among them, eight were scallop-specific EPl molecular species, occupying approximately 58% of the total area percentage of scallop EPls. Almost all large peaks contained 4, 5, or 6 unsaturated double bonds in the carbon chain at the sn-2 position of the glycerol backbone. Our results showed that EPls from scallops, lacking pituitary glands, stimulated both FSH and LH secretion by bovine gonadotrophs.
... However, little is known regarding global gene expression in the AP glands after aging. Unlike human AP glands, fresh bovine AP glands can be obtained as they can be collected from slaughterhouses (Kadokawa 2020;Kadokawa et al. 2021). Deep sequencing of the transcriptome (RNA-seq) via next-generation sequencing (NGS) technology is a recently developed high-throughput genetic analysis tool for determining global gene expression. ...
Proper functioning of the anterior pituitary (AP) gland is imperative, however, is suppressed by aging via unclear mechanisms. Therefore, we identified differentially expressed genes (DEGs) in the AP glands of Japanese Black young heifers (approximately 22 months old) compared to old cows (approximately 120 months old) via deep sequencing of the transcriptome (RNA-seq) to characterize potentially important pathways. The young and old AP glands expressed 20,171 annotated genes. Of the total transcripts per million, approximately 41.6% and 35.5% were the sum of seven AP hormone genes in young and old AP glands, respectively, with difference observed in the sum between the young and old AP glands (P < 0.05). Moreover, we identified 48 downregulated genes and 218 upregulated genes in old compared to young AP glands (P < 0.01, fold change > 120%). The DEGs included 1 cytokine (AIMP1), 3 growth factors (NRG2, PTN, and TGFB1), 1 receptor-associated protein gene (AGTRAP), and 10 receptor genes, including PRLHR and two orphan G-protein-coupled receptors (GPR156 and GPR176). Metascape analysis of the DEGs revealed “Peptide metabolic process,” “Regulation of hormone levels,” and “Peptide hormone processing” as enriched pathways. Furthermore, Ingenuity Pathway analysis of the DEGs revealed (1) a network of 24 genes (including GPR156 and PRLHR) named “Neurological disease, organismal injury and abnormalities, and psychological disorders”, and (2) two canonical pathways (P < 0.01), namely “Huntington’s disease signaling”, and “AMPK signaling”. Thus, the findings of the current study revealed relevant DEGs, while identifying important pathways that occur during aging in AP glands of female cattle.
... The anterior pituitary (AP) gland lies outside the blood-brain barrier [5], and may be affected by the virus [6]. Gonadotrophs are important cells located in the AP glands, and secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which regulate the testes, ovaries, and, via gonadal steroids, other reproductive organs in animals [7]. However, to the best of our knowledge, the effect of the virus on gonadotrophs remains unclear. ...
... Unlike human AP glands, bovine AP glands can be obtained for primary culture as they can be collected from slaughterhouses. Indeed, using bovine gonadotrophs, we discovered new receptors that control LH and FSH secretion, colocalizing with gonadotropin-releasing hormone (GnRH) receptor (GnRHR) in the lipid rafts of bovine gonadotrophs [7,11,12,13]. Bovine ACE2 contains most of the key residues for the receptor-binding domain of SARS-CoV-2 [14] (details are shown in Supplementary Fig.1), and SARS-CoV-2 replicates in bovine respiratory tissues [15]. Therefore, we tested the hypothesis that gonadotrophs express the spike protein receptor ACE2, colocalizing with GnRHR on the bovine gonadotroph cell surface, and that the recombinant spike protein suppresses LH and FSH secretion from cultured bovine AP cells. ...
... Cultured bovine gonadotroph cells express ACE2, and addition of recombinant spike protein to the culture medium suppressed the secretion of LH and FSH, providing clear evidence that the spike protein, containing both S1 (attachment to ACE2) and S2 (fusion with host membrane) regions, affects the cytoplasmic ERK pathways [9] that play important roles in the control of LH and FSH secretion [10]. ACE2 colocalizes with GnRHR on the lipid rafts of gonadotrophs [7], suggesting that the S2 region suppresses LH and FSH secretion by fusing with the lipid rafts [25] to affect heteromer receptors. ...
Coronavirus disease (COVID-19), the ongoing global pandemic, is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent evidence shows that the virus utilizes angiotensin-converting enzyme 2 (ACE2) as a spike protein receptor for entry into target host cells. The bovine ACE2 contains key residues for binding to the spike protein receptor-binding domain. This study evaluated the hypothesis that bovine gonadotroph expresses ACE2, and spike protein suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from cultured bovine anterior pituitary (AP) cells. ACE2 mRNA expression and ACE2 protein expression were detected in the bovine AP cells using reverse transcription PCR and western blot analysis. Immunofluorescence microscopy analysis with the anti-ACE2 antibody revealed the co-localization of ACE2 and gonadotropin-releasing hormone (GnRH) receptor on the gonadotroph plasma membrane. Approximately 90% of GnRH receptor-positive cells expressed ACE2, and approximately 46% of ACE2-positive cells expressed the GnRH receptor. We cultured bovine AP cells for 3.5 days and treated them with increasing concentrations (0, 0.07, 0.7, or 7 pM) of recombinant spike protein having both S1 and S2 regions. The spike protein (0.07–7 pM) suppressed both basal and GnRH-induced LH secretion (P < 0.05). Spike protein (0.7–7 pM) suppressed GnRH-induced (P < 0.05), but not basal FSH secretion. In contrast, pre-treatment with ERK 1/2/5 inhibitor (U0126) partially restored the GnRH-induced LH and FSH secretion from the spike protein suppression. Collectively, the results indicate that gonadotrophs express ACE2, a receptor for coronavirus 2 spike protein, which in turn suppresses LH and FSH secretion from AP cells.
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... After feeding the weaning gilts with a ZEA content of 596.86 μg/kg for 28 days, it was found that the vulva area increased significantly and the secretion of sex hormones was disordered . ZEA can bind to estrogen receptors in cells of target tissues, regulate the expression and synthesis of related genes and proteins and exert reproductive toxicity (Alm et al., 2002;Nikov et al., 2000;Aichinger et al., 2020;Kadokawa, 2020). Since the vulva is the target tissue of ZEA, so it can cause the vulva to enlarge. ...
The study aimed to examine the effects of zearalenone on genital organ development, serum immunoglobulin, antioxidant capacity, sex hormones and liver function of prepubertal gilts. Forty-eight prepubertal gilts (Landrace × Yorkshire) were randomly divided into three treatment (T1, T2 and T3) groups and a control group (12 replicates per group, 1 gilt per replicate). Prepubertal gilts in the control group were fed with basal diet, and those in T1, T2 and T3 groups were fed with basal diets supplemented with 200 μg/kg, 800 μg/kg and 1600 μg/kg zearalenone during the experiment period, which lasted for 14 d. Feed intake was counted and vulvar area was measured. The blood samples were collected from the anterior vena cava of 6 prepubertal gilts in each group, and immunoglobulins, antioxidant indexes, inflammatory cytokines, genital hormones, and biochemical indexes were analyzed by enzyme-linked immunosorbent assay. The results showed that the average daily feed intake of prepubertal gilts in each group had no significant change (p > 0.05). On 14 d, compared with the control group, the vulva area of prepubertal gilts in each treatment group was significantly increased (p < 0.05). Compared with the control group, the serum immunoglobulin G content in the T3 group was significantly reduced (p < 0.05). The activities of total antioxidant capacity and the superoxide dismutase of serum in the T3 group were significantly reduced (p < 0.05). Compared with the control group, the serum interleukin-4 content in each test group were extremely significantly increased (p < 0.01). The serum contents of luteinizing hormone in the T2 and T3 groups and estradiol in the T3 group were significantly reduced (p < 0.05) than that of control group. Compared with the control group, the activity of aspartate aminotransferase in T3 group was significantly increased (p < 0.05). In conclusion, zearalenone has no significantly effect on the feed intake of prepubertal gilts, but it can reduce its serum immunoglobulin contents and antioxidant properties, disrupt the secretion of sex hormones, increase the vulva area, produce reproductive toxicity and cause liver damage. Therefore, in pig production, the use of antimould reagent together with products of immunity-boosting, antioxidant, anti-inflammatory and hepatoprotective may enhance protection.
Alimentary infertility is becoming increasingly important due to the toxic effects of mycotoxins, especially zearalenone and deoxynivalenol, which leads to a decrease in the efficiency of the cattle breeding industry, so it is necessary to examine this problem. The purpose of the study was to identify the effect of the complex use of sorbents, acidifiers, and aromatase inhibitors on the reproductive capacity of cows in mycotoxicosis. During the study, clinical methods (general examination) and biochemical methods (serum content of calcium, magnesium, urea, total and direct bilirubin, malonic dialaldehyde, aminotransferase activity) were used. Cows were divided into two groups: the first group was a control group, where no treatment was used, and cows of the second group received a comprehensive treatment method. A decrease in the level of calcium to 1.68±0.53 mmol/L, phosphorus – 0.98±0.16, selenium – 0.64±0.1 mmol/L, an increase in the level of magnesium to 1.15±0.17 mmol/L, an increase in aspartate aminotransferase to 121.33±3.91 units, alataminotransferase to 79.31±6.53 units, and total bilirubin to 10.21±0.55 mmol/l, malone aldehyde up to 8.27±0.41 mmol/L, and ceruloplasmin up to mmol/L 2.14±0.39 in chronic mycotoxicosis caused by zearalenone and deoxynivalenol. When using a complex treatment regimen for animals, a substantial change and approximation to the reference levels of selenium, creatinine, AST, ALT, malonic aldehyde, and ceruloplasmin were established. The use of the proposed treatment regimen increases the fertilising capacity of cows after the 1st calving by 18.15%, cows aged 3-4 years – 30.12%, and cows of the older age group – by 40.47%. A complex method of treatment of cows for mycotoxicosis caused by zearalenone is proposed using an acidifier based on organic acids, a sorbent based on celeolite and an aromatase inhibitor, which can be used in livestock farms for the production of milk and meat of various forms of ownership to restore and normalise the reproductive ability of cows
Context:
Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls) are classes of ethanolamine ether phospholipids (ePE) and choline ether phospholipids (ePC), respectively. EPls play crucial roles in maternal and breastfed infant bodies and stimulate gonadotropin secretion by gonadotrophs.
Aims:
To estimate changes in and importance of plasma concentrations of EPls and CPls, utilising newly developed enzymatic fluorometric assays for ePE and ePC in postpartum Holstein cows.
Methods:
Plasma samples were collected from 3weeks before expected parturition until approximately 8weeks after parturition (16 primiparous and 38 multiparous cows) for analysis.
Key results:
Plasma concentrations of ePE and ePC, most of which are plasmalogens, declined before and increased after parturition and stabilised near the day of the first postpartum ovulation (1stOV). From weeks 2 to 3 after parturition, third-parity cows exhibited ePE concentrations that were higher than those of other parity cows. The days from parturition to 1stOV correlated with days from parturition to conception. On the day of 1stOV, milk yield correlated with plasma concentration of both ePE and ePC, while ePC concentration correlated negatively with milk fat percentage. At the early luteal phase after 1stOV, plasma ePE concentration correlated with plasma anti-Müllerian hormone concentration (r=0.39, P<0.01), and plasma ePC concentration correlated with plasma follicle-stimulating hormone concentration (r=0.43, P<0.01).
Conclusion:
The concentrations of ePE and ePC changed dramatically around parturition and 1stOV, and the concentrations correlated with important parameters for milk production and reproduction.
Implications:
The blood plasmalogen may play important roles in postpartum dairy cows.
