Hypothalamo-pituitary-gonadal Axis Research Articles

Intracerebroventricular injection of kisspeptin in male rats activates hypothalamo-pituitary-gonadal axis, but not hypothalamo-pituitary-adrenal axis

Kisspeptin is an important hormone involved in the stimulation of the hypothalamo-pituitary gonadal (HPG) axis. The HPG axis can be suppressed in certain conditions such as stress, which gives rise to the activation of the hypothalamo-pituitary-adrenal (HPA) axis. However, the physiological role of kisspeptin in the interaction of HPG and HPA axis is not fully understood yet. This study was conducted to investigate the possible effects of central kisspeptin injection on HPG axis as well as HPA axis activity. Adult male Wistar rats were randomly divided into seven groups as followed: sham (control), kisspeptin (50 pmol), P234 (1 nmol), kisspeptin + p234, kisspeptin + antalarmin (0.1 μg), kisspeptin + astressin 2B (1 μg), and kisspeptin + atosiban (300 ng/rat) (n = 10 each group). At the end of the experiments, the hypothalamus, pituitary, and serum samples of the rats were collected. There was no significant difference in corticotropic-releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone, and corticosterone levels among all groups. Moreover, no significant difference was detected in pituitary oxytocin level. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin, and kisspeptin + astressin 2B groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin kisspeptin + antalarmin, kisspeptin + astressin 2B, and kisspeptin + atosiban groups compared to the control group. Our findings suggest that central kisspeptin injection causes activation in the HPG axis, but not the HPA axis in male rats.

Severe mental illness and the perimenopause

Hormonal fluctuations in the perimenopause are associated with an array of physical and psychological symptoms. Those with pre-existing mental disorders may experience changes to their symptoms and response to treatment during the perimenopausal and postmenopausal periods and may also be at risk of poorer longer-term physical health outcomes in menopause. The transition towards menopause may be compounded by the oestradiol-suppressing effect of many psychotropics on the hypothalamopituitary–gonadal axis. A collaborative approach between primary care and secondary mental health services is an opportunity for proactive discussion of symptoms and support with management of the perimenopause. This may involve lifestyle measures and/or hormone replacement therapy, which can both lead to improvements in well-being and mental and physical health.

Investigation of irisin's role in pubertal onset physiology in female rats

ObjectiveThe timing of pubertal development is closely related to metabolic status and energy reserves. It is thought that irisin, which is involved in the regulation of energy metabolism and is shown to be present in the hypothalamo-pituitary-gonadal (HPG) axis, may play a role in this process. In our study, we aimed to investigate the effect of irisin administration on pubertal development and HPG axis in rats. Design-methods36 female rats were included in the study were divided into 3 groups: 100 ng/kg/day irisin treatment group (irisin-100), 50 ng/kg/day irisin treatment group (irisin-50), and control group. On the 38th day, serum samples were taken to determine levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and irisin. Brain hypothalamus samples were taken to determine levels of pulsatile gonadotropin-releasing hormone (GnRH), kisspeptin, neurokinin-B, dynorphin (Dyn), and makorin ring finger protein-3 (MKRN3). ResultsVaginal opening and estrus were seen firstly in the irisin-100 group. At the end of the study, the highest rate of vaginal patency was found in the irisin-100 group. Hypothalamic protein expression levels of GnRH, NKB and Kiss1 in homogenates; serum FSH, LH, and estradiol levels were the highest in the irisin-100 group, followed by the irisin-50 and control groups, respectively. Ovarian sizes were significantly greater in the irisin-100 group compared to the other groups. The hypothalamic protein expression levels of MKRN3 and Dyn were the lowest in the irisin-100 group. ConclusionsIn this experimental study, irisin triggered the onset of puberty in a dose-dependent manner. Irisin administration caused the excitatory system to dominate in the hypothalamic GnRH pulse generator.

Expression of phoenixin-14 and nesfatin-1 in the hypothalamo–pituitary–gonadal axis in the phases of the estrous cycle

Phoenixin-14 (PNX-14) and nucleobindin 2 (NUCB2)/nesfatin-1 are regulatory neuropeptides expressed in the hypothalamus. These neuropeptides can be effective in hormonal regulation of the hypothalamo–pituitary–gonadal (HPG) axis and reproductive functions. In the present study, the distribution of PNX-14 and NUCB2/nesfatin-1 in the hypothalamus, pituitary, ovary, and uterus tissues during the phases of the estrous cycle in female rats was investigated. Eighteen Wistar Albino rats determined among animals showing regular estrous cycle by vaginal smear method were divided into three groups: proestrus (Group I), estrus (Group II) and diestrus (Group III). Serum gonadotropin-releasing hormone (GnRH), plasma PNX-14, and NUCB2/nesfatin-1 concentrations were the highest, moderate, and lowest in estrus, diestrus, and proestrus phases, respectively. PNX-14 immunoreactivity in the supraoptic and arcuate nuclei of the hypothalamus and NUCB2/nesfatin-1 immunoreactivity in the paraventricular nuclei were particularly evident in the estrus phase. These neuropeptide immunoreactivities were decreased in different cells of anterior pituitary during proestrus compared with those during estrus and diestrus. PNX-14 immunoreactivity in the ovary, especially during the estrus phase, was diffuse and intense in the granulosa and luteal cells and oocytes, and it was few and weak in theca cells. In addition, NUCB2/nesfatin-1 immunoreactivity was abundant and strong in granulosa and luteal cells, theca and interstitial cells, and oocytes during estrus. In the estrus phase, PNX-14 immunoreactivity was strong in the glandular epithelial cells and stromal cells of the endometrium, also NUCB2/nesfatin-1 immunoreactivity was strong in the epithelial and glandular epithelial cells. As a result, when the estrous cycle was evaluated, it was concluded that the changes in the distribution of PNX-14 and NUCB2/nesfatin-1 at all phases were related to GnRH and that these neuropeptides showed the highest immunoreactivity especially in the HPG axis and uterus tissues of estrus rats.

The influence of COVID-19 infection-associated immune response on the female reproductive system†.

Coronavirus disease 2019 (COVID-19) is a multi-system disease that has led to a pandemic with unprecedented ramifications. The pandemic has challenged scientists for the past 2 years and brought back previously abandoned research topics. COVID-19 infection causes a myriad of symptoms ranging from mild flu-like symptoms to severe illness requiring hospitalization. Case reports showed multiple systemic effects of COVID-19 infection, including acute respiratory distress syndrome, fibrosis, colitis, thyroiditis, demyelinating syndromes, and mania, indicating that COVID-19 can affect most human body systems. Unsurprisingly, a major concern for women all over the globe is whether a COVID-19 infection has any long-term effects on their menstrual cycle, fertility, or pregnancy. Published data have suggested an effect on the reproductive health, and we hypothesize that the reported reproductive adverse effects are due to the robust immune reaction against COVID-19 and the associated cytokine storm. While the COVID-19 receptor (angiotensin converting enzyme, ACE2) is expressed in the ovaries, uterus, vagina, and placenta, we hypothesize that it plays a less important role in the adverse effects on the reproductive system. Cytokines and glucocorticoids act on the hypothalamo-pituitary gonadal axis, arachidonic acid pathways, and the uterus, which leads to menstrual disturbances and pregnancy-related adverse events such as preterm labor and miscarriages. This hypothesis is further supported by the apparent lack of long-term effects on the reproductive health in females, indicating that when the cytokine storm and its effects are dampened, the reproductive health of women is no longer affected.

Effects of kisspeptin-10 on the reproductive performance of sows in a fixed-time artificial insemination programme

Kisspeptin (KP) is a major positive regulator of the hypothalamo–pituitary–gonadal axis and affects female reproductive cyclicity in mammals. It offers an attractive alternative strategy to control reproduction in fixed-time artificial insemination (FTAI) protocols. We aimed to evaluate the effects of different doses of kisspeptin-10 (KP-10) on sow reproductive performance in FTAI protocols. One hundred ninety-eight weaned sows were divided into three groups at random. A FTAI–GnRH group of sows (n = 98) received 100 µg (2 mL) gonadotropin-releasing hormone (GnRH; gonadorelin) by intramuscular injection at 96 h after weaning (t = 0 h); FTAI–KPL (KPL: low-dose KP-10, n = 50), and FTAI–KPH groups of sows (KPH: high-dose KP-10, n = 50) received 0.5 or 1 mg KP-10 (2 mL) respectively at 96 h after weaning. Sows were checked twice daily for oestrus. Ultrasonographic evaluations were performed to determine the follicular diameter and time of ovulation; blood samples were collected immediately before injection (t0 = 0 min) and at 15, 30, 45, 60, 75, 90 min, 24 and 48 h postinjection. Sows were inseminated at 112 and 132 h after weaning. The oestrus rates (96 vs 92%; 96 vs 88%) and weaning-to-oestrus intervals (98.9 vs 98.6 h; 98.9 vs 97.1 h) were not affected by treatment, but oestrus in the FTAI–KPL group was significantly longer than in the FTAI–GnRH group (38.7 vs 30.0 h; P < 0.05). The peak LH concentrations were 1.29 times greater than at t0 = 0 in the FTAI–GnRH group, and 1.45 and 1.44 times greater than at t0 = 0 in the FTAI–KPL and FTAI–KPH groups, respectively. Follicular diameters and pregnancy rates (86 vs 88%, 86 vs 80%, respectively) did not differ between the treatments. Moreover, the total numbers of piglets born and those born alive did not differ among the three groups. These findings suggested that 0.5 mg KP-10 given at 96 h after weaning could be used in FTAI programmes to manage batch farrowing in sows.

Gonadotropin-releasing hormone-secreting neuron development and function: an update.

The coordinated and pulsatile secretion of gonadotropin-releasing hormone (GnRH) plays a central role in vertebrate reproductive function. The development of the hypothalamo-pituitary-gonadal (HPG) axis is characterized by a complex network of molecular signals that controls, at first, migration of the GnRH neurons along the nose, through the cribriform plate, up to the frontal lobe. This migratory process is orchestrated by several factors including anosmin-1, polysialylated form of the neural cell adhesion molecule, γ-amino butyric acid, hepatocyte growth factor, chemokines, cytokines and semaphorins. Moreover, antimüllerian hormone, growth hormone and insulin-like growth factor-1 were recently reported to modulate immature GnRH neuron migration in vitro. Once arrived in the forebrain, GnRH neurons mainly localize in the medial preoptic area and their axon elongation, mediated by fibroblast growth factor receptor 1 and semaphorin 7A signaling, is essential for GnRH secretion. The physiological pulsatile release of GnRH is controlled by central and peripheral factors, including kisspeptin, neurokinin B and dynorphin from KNDy neurons, and sex steroids and leptin, respectively. GnRH pulsatile release into the hypothalamus-pituitary blood portal system stimulates luteinizing hormone and follicle-stimulating hormone secretion into the general circulation. Such knowledge also results crucial for understanding of the molecular bases of congenital and acquired dysfunction of the HPG axis, which imply severe pathological consequences, such as GnRH deficiency or congenital hypogonadotropic hypogonadism, characterized by incomplete or absent puberty and infertility.

A review of scrotal temperature regulation and its importance for male fertility

Male fertility is a very important but often neglected area in medical practice. Compared to what is available on female subfertility, there is a dearth in research on male fertility. Fertility in male depends on the normally functioning hypothalamopituitary gonadal axis, normal testis and the environment necessary for viable, motile sperm production. The production of healthy germ cells require a temperature which is slightly below the core body temperature and there are several temperature regulatory mechanisms in humans that ensure the maintenance of the scrotal temperature several degrees lower. The aim of the present review is to synthesise and summarise the literature available on scrotal temperature regulation in the healthy male and to recapitulate the disease conditions, environmental, occupational and lifestyle factors that affects scrotal temperature and thus male fertility.

Stress and steroid interaction modulates expression of estrogen receptor alpha in the brain, pituitary, and testes of immature Gallus gallus domesticus

In nature, food availability stimulates hypothalamo-pituitary-gonadal (HPG) axis while its scarcity induces stress, which further stimulates hypothalamo-pituitary-adrenal (HPA) axis producing a detrimental effect on the avian reproductive physiology. The present experiment was designed to examine the interaction of stress like food restriction and estradiol on male reproductive physiology with special emphasis on estrogen receptor alpha (ERα) as these play crucial role in reproduction. To achieve this, 60 day old White Leghorn immature cockrels were taken and divided into four groups (n = 8 per group). One group was provided with food and water ad libitum. Second group was food restricted (FR) for 9 h/day after 5 days, third and fourth were administered with estradiol benzoate (EB 0.5 mg/100g/day) for 12 days. Fourth group was FR for 9 h/day after 5 days of EB treatment till last day of experiment (EB + FR). Immunofluorescent localization of ERα was principally in the pre-optic area and paraventricular nuclei of hypothalamus and in anterior pituitary gland. ERα expression was highly reduced (from 40 AU to 20 AU) after FR in testis but it increased (50 AU) after EB administration, EB + FR reflects a diminishing pattern in the increment after EB. FR decreased plasma estradiol while EB increased it. Increased plasma corticosterone, hydrogen peroxide, malondialdehyde, and decreased anti-oxidant enzymes in brain and testis of all groups indicate oxidative stress in the HPG axis. The increased ERα after EB and a decrease with FR and EB + FR support their reproductive function. Estrogen and its receptor alpha are responsible for maintaining epithelial morphology but FR along with EB administration modulates the testicular development by significantly decreasing its size (p<.0001) and seminiferous tubules (p<.0001) and no sperm formation via highly reduced expression of ir-ERα in HPG axis. Our findings led us to conclude that stress like FR and estradiol induces testicular regression immature male chickens by modulating ir-ERα expression in the HPG axis thereby resulting in reduction in reproductive physiology

Mechanisms of Central Hypogonadism.

Reproductive function depends upon an operational hypothalamo–pituitary–gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.

Field study reveals morphological and neuroendocrine correlates of seasonal breeding in female water voles, Arvicola terrestris

Seasonally breeding mammals display timely physiological switches between reproductive activity and sexual rest, which ensure synchronisation of births at the most favourable time of the year. These switches correlate with seasonal changes along the hypothalamo-pituitary–gonadal axis, but they are primarily orchestrated at the hypothalamic level through environmental control of KISS1-dependent GnRH release. Our field study shows that births of fossorial water voles, Arvicola terrestris, are concentrated between March and October, which indicates the existence of an annual reproductive cycle in this species. Monthly field monitoring for over a year further reveals dramatic seasonal changes in the morphology of the ovary, uterus and lateral scent glands, which correlate with the reproductive status. Finally, we demonstrate seasonal variation in kisspeptin expression within the hypothalamic arcuate nucleus. Altogether, this study demonstrates a marked rhythm of seasonal breeding in the water vole and we speculate that this is governed by seasonal changes in photoperiod.

Effect of age at first egg on reproduction performance and characterization of the hypothalamo–pituitary–gonadal axis in chickens

As an important indicator of sexual maturity of hens, age at first egg (AFE) is significantly associated with reproduction performance. In this study, 400 hens were divided into 6 groups based on AFE to analyze the difference of reproduction performance, reproduction hormone levels and the characterization of the hypothalamo–pituitary–gonadal axis in chickens. The results showed that the egg production of the hens in the late-maturing groups was significantly lower than that of the ones in other groups and the precocious hens had a lower egg production rate. The hens in late-maturing group had a lower fertility rate, LH levels and shorter duration of peak of egg production (PEP), the precocious hens had lower PRL levels. In addition, the characterization of the hypothalamo–pituitary–gonadal axis showed that the individuals with normal AFE had higher GNRH, GNRHR, ESR1, KITLG, and CYP11A1 expression levels than late-maturing and precocious individuals, which indicated that the chickens with normal AFE advantages on reproduction regulation system.

Immunological interpretation of minipuberty: Minipuberty as the driving force of sexual dimorphism in the immune response.

Although the physiology of minipuberty is well established, it is not fully explained why it occurs. It has been suggested that minipuberty contributes to the development of reproductive organs, somatic growth, cognitive/behavioural and sex-specific brain development. Given the well-known trade-off between the reproductive/endocrine and immune systems in adults, the immunological approach to minipuberty, which is characterized by transient activation of the hypothalamo-pituitary gonadal (HPG) axis, seems to be ignored. This study focused on the relationship of the lymphocyte subsets with gonadotrophin and sex hormones during the minipuberty. A total of 121 newborns (58 male) were included in this cross-sectional study. The hormone and lymphocyte subsets studied were as follow: follicle-stimulating hormone (FSH), luteinizing hormone (LH) estradiol (E), testosterone (T), CD19, CD16/56, CD3, CD3/CD4, CD3/CD8 and HLA-DR as lymphocyte activation marker. The mean FSH levels were higher in females (15.15±10.12mIU/ml vs, 2.61±1.74mIU/ml) and LH in males (5.80±2.51mIU/ml vs. 1.91±12.89mIU/ml) (P<.001 for each). The mean percentages of the CD3/CD4 levels were higher in females (54.61±6.70% vs. 51.17±6.77%) and CD3/CD8 in males (21.49±4.82% vs. 17.31±3.66%) (P<.001 for each). In the females, the mean FSH levels negatively correlated with CD3/CD4 (rFSH-CD3/CD4 =-0.423, P=.001) and positively correlated with CD3/CD8 (rFSH-CD3/CD8 =0.311, P=.013). In the males, LH positively correlated with CD3/CD4 (rLH-CD3/CD4 =0.406, P<.001) and negatively correlated with CD3/CD8 (rLH-CD3/CD8 =-0.486, P<.001). This study showed that the mean CD3/CD4 levels were higher in female and CD3/CD8 in male newborns, indicating that there was a sexual dimorphism in favour of immunostimulant in females and immunosuppressor components of immune response in males during the minipuberty. These interactions point to sex-specific trade-off between reproductive/endocrine and immune systems, which it reflects the an investment favouring in the reproductive system against the immune response during minipuberty, which is critical period for adult fertility, especially in males.

Transcriptome analysis of the hypothalamus and pituitary of turkey hens with low and high egg production

BackgroundHigh egg producing hens (HEPH) show increased hypothalamic and pituitary gene expression related to hypothalamo-pituitary-gonadal (HPG) axis stimulation as well as increased in vitro responsiveness to gonadotropin releasing hormone (GnRH) stimulation in the pituitary when compared to low egg producing hens (LEPH). Transcriptome analysis was performed on hypothalamus and pituitary samples from LEPH and HEPH to identify novel regulators of HPG axis function.ResultsIn the hypothalamus and pituitary, 4644 differentially expressed genes (DEGs) were identified between LEPH and HEPH, with 2021 genes up-regulated in LEPH and 2623 genes up-regulated in HEPH. In LEPH, up-regulated genes showed enrichment of the hypothalamo-pituitary-thyroid (HPT) axis. Beta-estradiol was identified as an upstream regulator regardless of tissue. When LEPH and HEPH samples were compared, beta-estradiol was activated in HEPH in 3 of the 4 comparisons, which correlated to the number of beta-estradiol target genes up-regulated in HEPH. In in vitro pituitary cell cultures from LEPH and HEPH, thyroid hormone pretreatment negatively impacted gonadotropin subunit mRNA levels in cells from both LEPH and HEPH, with the effect being more prominent in HEPH cells. Additionally, the effect of estradiol pretreatment on gonadotropin subunit mRNA levels in HEPH cells was negative, whereas estradiol pretreatment increased gonadotropin subunit mRNA levels in LEPH cells.ConclusionsUp-regulation of the HPT axis in LEPH and upstream beta-estradiol activation in HEPH may play a role in regulating HPG axis function, and ultimately ovulation rates. Thyroid hormone and estradiol pretreatment impacted gonadotropin mRNA levels following GnRH stimulation, with the inhibitory effects of thyroid hormone more detrimental in HEPH and estradiol stimulatory effects more prominent in LEPH. Responsiveness to thyroid hormone and estradiol may be due to desensitization to thyroid hormone and estradiol in LEPH and HEPH, respectively, due to up-regulation of the HPT axis in LEPH and of the HPG axis in HEPH. Further studies will be necessary to identify possible target gene desensitization mechanisms and elicit the regulatory role of the HPT axis and beta-estradiol on ovulation rates in turkey hens.

Differences in invitro responses of the hypothalamo–pituitary–gonadal hormonal axis between low- and high-egg-producing turkey hens

Low-egg-producing hens (LEPH) ovulate less frequently than high-egg-producing hens (HEPH) and exhibit differences in mRNA levels for components of the hypothalamo–pituitary–gonadal (HPG) axis, suggesting differential responsiveness to trophic stimulation. Ovulation frequency is governed by the production of the pituitary gonadotropins and feedback of the ovarian follicle steroid hormones, which are regulated by HPG axis stimulation and inhibition at the hypothalamic level. The pituitary and follicle cells from LEPH and HEPH were subjected to in vitro hormonal treatments to stimulate or inhibit the HPG axis, followed by expression analysis of mRNA levels for HPG axis genes and radioimmunoassays for steroid hormone production. Statistical analysis was performed using the mixed models procedure of SAS. The pituitary cells from HEPH showed upregulation of genes associated with ovulation stimulation, whereas cells from LEPH showed upregulation of genes associated with inhibition of ovulation. High-egg-producing hens’ follicle cells displayed a higher sensitivity and responsiveness to gonadotropin treatment. Level of egg production impacted ovulation-related gene expression in the pituitary cells as well as steroid hormone production in the follicle cells, with HEPH displaying a greater positive response to stimulation. These findings indicate that differences in egg production among turkey hens likely involve differential responsiveness of the cells within the HPG axis.

Effect of estrogen and stress on estrogen receptor 1 in the HPG axis of immature male Gallus gallus domesticus: Involvement of anti-oxidant system

Estrogen plays a key role in the regulation of reproductive behavior and control of the neuroendocrine system in both males and females. However, excessive quantity of exogenous estrogen produces a deleterious effect on the male reproductive system. To elucidate the mechanism by which estrogen modulates its receptor alpha (ESR1) in immature chicken during stress the study has been undertaken. The experiment investigated the physiological changes in the abundance of ESR1 in brain, pituitary and testes of immature male chickens after stress like water restriction. Twenty four immature male chickens were randomly assigned into four groups. The control group was provided with food and water ad libitum, second was water restricted 9 h each day for seven days (WR), third was treated with estradiol benzoate (EB) and fourth group was treated with EB followed by water restriction during last seven days of treatment (EB + WR). EB was administered at a dose of 0.5 mg/100 g/day for 12 days. EB administration as well as WR increases both the H2O2 and Malondialdehyde levels indicating oxidative stress in brain as well as in testis. Plasma corticosterone significantly increased in all groups while estradiol significantly decreased after water restriction. ESR1 protein was detected by immuno-fluorescence predominantly in the pre-optic area of the hypothalamus, pituitary and testes after EB administration. EB administration increases ESR1 proteins abundantly in the Sertoli cells, Leydig cells, spermatogonia and spermatids while WR decreases it. The decline in ESR1 proteins after EB administration during stress appears to be mediated by interaction of estrogen with hypothalamo-pituitary-adrenal (HPA) axis. Therefore, the findings substantiate the fact that WR and EB treatment increase the stress and alter the anti-oxidant enzymes via its receptor ESR1 in the brain, pituitary and testis of immature chicks. Moreover, these findings highlight the effect of estradiol in male chicks causing stress which is disrupting the normal physiological feedback mechanism in hormone release and the expression of receptor ESR1 along the hypothalamo-pituitary-gonadal (HPG) axis.

Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay.

Plants are a source of food for many animals, andthey can produce thousands of chemicals. Some of these compounds affect physiological processes in the vertebrates that consume them, such as endocrine function. Phytoestrogens, the most well studied endocrine-active phytochemicals, directly interact with the hypothalamo-pituitary gonadal axis of the vertebrate endocrine system. Here we present the novel use of a cell-based assay to screen plant extracts for the presence of compounds that have estrogenic biological activity. This assay uses mammalian cells engineered to highly express estrogen receptor beta (ERβ) and that have been transfected with a luciferase gene. Exposure to compounds with estrogenic activity results in the cells producing light. This assay is a reliable and simple way to test for biological estrogenic activity. It has several improvements over transient transfection assays, most notably, ease of use, the stability of the cells, and the sensitivity of the assay.

Inhibin B as a screening tool for early detection and treatment monitoring of central precocious puberty

Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1 year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59 pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.

Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose?

Objective:Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose.Methods:Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate.Results:Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001).Conclusion:Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.

Characterization of the hypothalamo–pituitary–gonadal axis in low and high egg producing turkey hens

Variation in egg production exists in commercial turkey hens, with low egg producing hens (LEPH) costing more per egg produced than high egg producing hens (HEPH). Egg production correlates with ovulation frequency, which is governed by the hypothalamic–pituitary–gonadal (HPG) axis. Ovulation is stimulated by a preovulatory surge (PS) of progesterone and luteinizing hormone, triggered by gonadotropin releasing hormone release and inhibited by gonadotropin inhibiting hormone. Differences between LEPH and HEPH were characterized by determining HPG axis plasma hormone profiles and mRNA levels for key genes, both outside and inside of the PS (n = 3 per group). Data were analyzed with a 2-way ANOVA using the mixed models procedure of SAS. In the HPG axis, plasma progesterone levels were not affected by egg production level but were elevated during the PS. In contrast, plasma estradiol levels were higher in HEPH than in LEPH but were not associated with the PS. LEPH exhibited decreased gene expression associated with ovulation stimulation and increased gene expression associated with ovulation inhibition in the hypothalamus and pituitary. In ovarian follicle cells, LEPH displayed decreased gene expression associated with progesterone, androgen, and estradiol production in the F1 follicle granulosa cells, F5 theca interna cells, and small white follicle cells, respectively. Different degrees of stimulation and inhibition within all tissues of the HPG axis were noted between LEPH and HEPH turkey hens, with HEPH showing higher expression of genes related to ovulation and steroidogenesis.