Hypothalamic-pituitary-gonadal Axis Research Articles

Role of hypothalamic-pituitarygonadal regulatory axis in growth of melanoma В16/F10 in С57/BL6 mice

Aim: to study the role of the hypothalamic-pituitary-gonadal (HPG) regulatory axis and its dermal analogue in C57BL/6 mice of both sexes with the growth of B16/F10 grafted melanoma. The studies were carried out in mice of both sexes of the C57BL/6 line, which were transplanted with B16/F10 melanoma by subcutaneous injection of 0.5 ml of a suspension of tumor tissue. In intact animals and in the animals 14 days after the tumor inoculation, the levels of gonadal releasing hormone (GnRH), LH and FSH, and estradiol (E2), total testosterone (T) and free testosterone (Tfr), progesterone (P4), as well as ERα and ERβ estrogen receptors, progesterone receptor (RP4) and androgen receptor (RA) were determined. Results. In the males, compared with the females, after melanoma transplantation, the latent period and average life spans were shorter, while their tumor volumes were larger. A 2.1-fold decrease in GnRH in the hypothalamus in males led to a 2.7- fold increase in the level of LH in the pituitary gland, while in females a 1.4-fold (p<0.05) increase in GnRH promoted an increase in LH and FSH in the pituitary gland by 3.4-2.7 times. The blood serum did not adequately reflect changes in hormones in the central and peripheral links. In females, only in their tumor samples, an increased content of GnRH, LH, FSH and sex hormone receptors was revealed, while in males, the level of regulatory peptides and some receptors also increased in the skin. The change in the activity of the HPG axis in the logarithmic phase of the growth of B16/F10 grafted melanoma had its gender specifics and was characterized by a disorder in the direct and reverse feedback loops. Melanoma contained in an increased amount of all the regulatory peptides, hormones and receptors of the HPG axis, which allowed it to provide autonomous regulation of its own growth.

Differences in the functioning of the hypothalamic-pituitarygonadal axis of regulation in male rats at one (liver) site and two (liver and lungs) sites of metastasis of sarcoma 45 in the experiment

Aims: to study the features of the functioning of the hypothalamic-pituitary-gonadal axis (HPGA) regulation in male rats at the stages of liver metastasizing. Materials and methods. Our research work was performed in 30 outbred male rats. Metastases in the liver were produced by implantation of sarcoma 45 (S45) cells into the spleen, which was previously positioned under the skin. The time spans of the study are 5 weeks (the pre-metastatic stage) and 7 weeks (the metastatic stage) after tumor cell transplantation. In the tissues, the content of the following hormones was determined by RIA: luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (Ttot), progesterone (P4); by ELISA we determined the content of the following hormones: gonadotropin-releasing hormone (GnRH), free testosterone (Tfr) and estrone (E1). Results. At all stages of the study, the level of GnRH in the hypothalamus decreased by more than 2.0 times; in the pituitary gland, the hormone levels had multidirectional dynamics: LH decreased by 1.6 times, and FSH increased by more than 6.0 times. Liver metastases were characterized by high levels of E1 and Ttot. In the gonads, a high level of P4 was recorded and concentrations of both forms of testosterone were reduced. The concentrations of E2 (by 1.6 times), Tfr (by 4.8 times) increased in blood, and the level of Ttot decreased (by 1.9 times). The salient features of HPGA in the presence of two metastasis sites (liver and lungs) were as follows: in blood, a 2.0 times lower increase in the LH and Tfr contents, a 1.6 times greater increase in E2, an increase in P4 (2.6 times), 1, 4 times lower level of FSH; in the gonads, there are found lower levels of P4, E1, but higher levels of Tfr and Ttot; in liver metastases, a greater increase in P4 (5.2 times), E1 (2.2 times) and Tfr (2.0 times) is recorded. Conclusion. Metastasizing to the liver was accompanied by activation of HPGA with the maximum accumulation of reactogenic E1 in liver metastases in rats with two metastasis sites that may indicate their more severe malignancy and ability to metastasize to the lungs.

Disorders in connections of the hypothalamic-pituitarygonadal axis in rats with Guerin’s carcinoma against the background of induced hypothyroidism

Aims: to study the content of regulatory peptides in the hypothalamus and pituitary gland, as well as sex steroids in the gonads in rats of both sexes with Guerin’s carcinoma against the background of hypothyroidism. Materials and methods. Our experiment was performed in white outbred rats of both sexes with induced hypothyroidism, against the background of which Guerin’s carcinoma was transplanted. In 1% homogenates of the pituitary and the hypothalamus and in 10% homogenates of the gonads in the animals from the main and reference groups, the levels of GnRH (Casabio, China) were determined by the ELISA method using standard kits, and the content of LH, FSH, estradiol (E2), testosterone (T) and progesterone (P4) by the RIA method (Immunotech, Czech Republic). Statistical analysis of the results was performed using the Statistica 10.0 software package. Results. In females of the main group, the level of GnRH in the hypothalamus increased by 1.6 times, but the content of LH and FSH in the pituitary gland decreased, while in males the content of GnRH decreased by 1.4 times and FSH by 1.6 times compared with the intact animals. In the gonads of females of the main group, the content of E2 and T decreased by 1.3 times, but the level of P4 increased by 4.7 times, while in males the T production decreased by 7.1 times. Hypothyroidism, against the background of which Guerin’s carcinoma developed, had a significant effect both on the central links of the HPG axis and the peripheral ones, producing an additional hormonal imbalance in sex steroids

Delayed Puberty.

Testicular volume ≥4ml and appearance of breast budding are the first signs of puberty. Delayed puberty is diagnosed in the absence of thelarche by 13 y or menarche by 15 y in girls and absence of testicular enlargement by 14 y in boys. Delayed puberty can be due to hypogonadotrophic hypogonadism, hypergonadotrophic hypogonadism or eugonadotrophic eugonadism characterised by low, elevated and normal gonadotrophin levels, respectively. Constitutional Delay of Growth and Puberty (CDGP) and systemic illness should be considered before pathological causes. Assessment of sexual maturity by Tanner's staging and anthropometric assessment on growth chart is pivotal. Lack of menarche in girls with thelarche suggests structural abnormalities of reproductive tract or disorders of sexual development. Measurement of bone age helps to interpret hormone measurements and decide on timing of pubertal induction. Ultrasound assessment of abdomen gives valuable clues to pubertal onset (in girls) and possible underlying etiology. Karyotyping is mandatory in all girls with delayed puberty and short stature, and delayed menarche and boys with hypergonadotrophic hypogonadism. Gonadotrophin releasing hormone analogue stimulation test may help distinguish hypogonadotrophic hypogonadism from CDGP. Pubertal induction is done with intramuscular testosterone and oral estradiol in boys and girls, respectively. Hormone replacement is begun at low doses and slowly escalated over 2 y to mimic a physiological puberty process. Short course of testosterone for 3 to 6 mo is helpful in adolescent boys with CDGP and psychological distress. Attainment of adult sexual maturity by 18 y is mandatory to rule out disorders of hypothalamic pituitary gonadal axis.

Hypogonadism in men with obstructive sleep apnea and its related risk factors

Background Sleep-related breathing disorders, including obstructive sleep apnea (OSA), have been linked to altered hypothalamic–pituitary–gonadal axis. Hypoxia, sleep fragmentation. and decreased deep sleep time in patients with OSA affect the hypothalamic–pituitary–gonadal axis, including serum luteinizing hormone (LH) and testosterone levels. Purpose To study serum levels of LH and testosterone in men with OSA and to investigate the possible risk factors that could affect their levels. Patients and methods This was a prospective cohort case–control study. The case group included 16 adult patients diagnosed with OSA confirmed by polysomnography. The control group included 16 matched healthy participants. Both groups were subjected to history taking, clinical examination, and investigations, including the Epworth sleepiness scale, BMI, neck circumference measurement, and serum levels of LH and testosterone. Results Patients with OSA had significantly higher mean levels of serum LH compared with healthy controls (P=0.031). The mean serum level of testosterone was lower in the OSA group compared with the matched controls; however, this difference was statistically insignificant (P=0.192). Among the studied risk factors for altered hormonal levels in patients with OSA, there was a significant positive correlation between desaturation index and serum LH levels (P=0.046) and a significant negative correlation between Epworth sleepiness scale and serum testosterone levels (P=0.025). Conclusion Our findings suggest that OSA in men is associated with a dysfunction in the hypothalamic–pituitary–gonadal axis, represented as high levels of serum LH. Although serum levels of testosterone were lower in patients with OSA, the study was underpowered to show a statistically significant difference.

Bifidobacterium supplementation attenuates hypercholesterolemia induced gut-brain-testis dysfunction in a rat model

Hypercholesterolemia is the state of high LDL blood cholesterol levels. This may lead to cholesterol accumulation in organs and cause diseases such as male infertility and NAFLD. Recent studies have shown strong correlations between Bifidobacterium strains and plasma cholesterol reduction. Bifidobacterium species are gram positive bacteria known to colonize the human gastrointestinal tract. Studies suggest that Bifidobacterium may reduce serum cholesterol levels by increasing bile salt hydrolase (BSH) activity. BSH increases fecal excretion of bile salt, and to compensate the loss of circulating bile acids, productions of bile acids using cholesterol are promoted. Currently, medications such as statins are commonly used. However, long term consumption could cause adverse effects on male reproductive organs. Bifidobacterium strains are known to regulate the hypothalamus-pituitary-gonadal (HPG) axis by modulating gut microbiota . Gut microbial bacteria such as Bifidobacterium contribute to the host metabolism by enhancing gut barrier integrity, reducing inflammation cytokine expressions, and increasing metabolite productions such as short chain fatty acids (SCFAs). Particularly, SCFAs like butyrate can cross the blood-brain barrier, and consequently affect the HPG axis. This suggests that Bifidobacterium strains may lower serum cholesterol while protecting reproductive organs. Therefore, this study aimed to evaluate and compare the serum cholesterol lowering and HPG axis protecting effects of Bifidobacterium strains with statin in the gut-brain-testis axis of a high cholesterol diet (HCD) induced hypercholesterolemia rat model. 6-week oral gavage of Bifidobacterium strains known to have BSH activity effectively reduced serum total cholesterol and LDL cholesterol levels in rats given HCD for the same period. Moreover, serum inflammatory cytokine IL-1β was reduced by Bifidobacterium treatment. Bifidobacterium also exerted protective effects against intestinal, testicular, and cerebral damage by attenuating disruption of histology and modulating transcript levels of inflammation markers. Notably, Bifidobacterium alleviated the HCD-induced reduction of male sex hormone synthesis markers in the testis, which statin had no effect. Fecal analysis revealed that Bifidobacterium treatment modulates gut microbiota compositions and metabolite levels such as SCFAs. Particularly, 16s rRNA genomic annotation showed that Bifidobacterium strains may have specific functions related to cholesterol reduction. Altogether, Bifidobacterium supplementation may reduce serum cholesterol levels by altering gut microbiota compositions, which affect gut metabolite compositions, inflammatory markers, and sex hormone synthesis markers. In conclusion, Bifidobacterium supplementation is a potential therapeutic approach for hypercholesterolemia-induced intestine, brain, and testis dysfunction. This work was supported by Cellbiotech Co., Ltd. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pre- and postnatal developmental exposure to the polychlorinated biphenyl mixture aroclor 1221 alters female rat pituitary gonadotropins and estrogen receptor alpha levels

Polychlorinated-biphenyls (PCBs) are industrial compounds, which were widely used in manufacturing of electrical parts and transformers. Despite being banned in 1979 due to human health concerns, they persist in the environment. In humans and experimental model systems, PCBs elicit toxicity in part by acting as endocrine-disrupting chemicals (EDCs). Aroclor 1221 (A1221) is a weakly estrogenic PCB mixture known to alter reproductive function in rodents. EDCs can impact hormone signaling at any level of the hypothalamic-pituitary-gonadal (HPG) axis, and we investigated the effects of A1221 exposure during the prenatal and postnatal developmental periods on pituitary hormone and steroid receptor expression in female rats. Examining offspring at 3 ages, postnatal day 8 (P8), P32 and P60, we found that prenatal exposure to A1221 increased P8 neonate pituitary luteinizing hormone beta (Lhb) mRNA and LHβ gonadotrope cell number while decreasing LH serum hormone concentration. No changes in pituitary hormone or hormone receptor gene expression were observed peri-puberty at P32. In reproductively mature rats at P60, we found pituitary follicle stimulating hormone beta (Fshb) mRNA levels increased by prenatal A1221 exposure with no corresponding alterations in FSH hormone or FSHβ expressing cell number. Estrogen receptor alpha (ERα) mRNA and protein levels were also increased at P60, but only following postnatal A1221 dosing. Together, these data illustrate that exposure to the PCB A1221, during critical developmental windows, alters pituitary gonadotropin hormone subunits and ERα levels in offspring at different phases of maturation, potentially impacting reproductive function in concert with other components of the HPG axis.

Strategies to Increase Testosterone in Men Seeking Fertility.

Prevalence of testosterone deficiency is increasing in the adolescent and young adult male population. As the average paternal age rises, there is a significant population of men with hypogonadism seeking testosterone therapy wishing to achieve or maintain fertility potential. Identification of potential lifestyle modifications that may improve the testosterone deficiency is one of the initial interventions of the holistic strategy in treatment. This is followed by drug therapy; however, traditional testosterone therapy acts as a contraceptive by suppressing the hypothalamus-pituitary-gonadal (HPG) axis and therefore cannot be used as a treatment strategy. A solution has been the off-label use of selective estrogen receptor modulators, human chorionic gonadotropin (hCG), and anastrozole inhibitors to treat hypogonadal symptoms while increasing intratesticular testosterone, a necessity for spermatogenesis. Recently, a novel therapy, Natesto intranasal testosterone gel, has been shown to increase serum testosterone levels while maintaining semen parameters. This is hypothesized to be because of its short-acting properties having lesser effect on the HPG axis, in contrast to the long-acting properties of traditional testosterone therapy. It is important to differentiate hypogonadal men between those seeking to achieve or maintain fertility status because the drug therapy of choice differs. This can be accomplished by determining the levels of 17-hydroxyprogesterone (17-OHP), because it is a biomarker for intratesticular testosterone. Those with low 17-OHP may wish to initiate treatment with alternative therapies, whereas those with high 17-OHP may trial short-acting testosterone therapies. As the urologist's armamentarium continues to increase, better strategies to increase testosterone levels in men seeking fertility can be achieved.

Long COVID and risk of erectile dysfunction in recovered patients from mild to moderate COVID-19

Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Gonadotropin-Releasing Hormone Studies to Assess Pubertal Deficiencies in Prader-Willi Syndrome

Patients with Prader-Willi Syndrome (PWS) are known to have variable pubertal development with most having delayed or incomplete puberty. This study aims to evaluate the activity of the Hypothalamic-Pituitary-Gonadal (HPG) axis in individuals with PWS. Thirty-five patients (18 males, 17 females) ages ranging from 3 to 38 years with genetically verified PWS underwent GnRH stimulation testing using gonadorelin along with clinical evaluations. Of patients in the typical age range for initiation of puberty, six had LH peak >5IU/L, indicating activation, but the remaining six had variable peaks, indicating lack of, or indeterminate activation. In some females, physical examination noted breast development to Tanner stage II to III, despite apparent lack of HPG axis activation, while in some males testicular volumes were smaller than expected despite apparent activation of the HPG axis. We studied genotype differences (deletion vs UPD) with respect to HPG axis activation. Mean LH levels were nearly double for PWS females with UPD compared to PWS females with deletion. Both peak LH and peak FSH levels appear to be higher in males with deletion compared to UPD. Inconsistency between physical examination and stimulation testing results and the high variability in the age at activation of the HPG axis accentuates the need for the evaluation of pubertal staging in patients with PWS, and consideration of sex-steroid supplementation.

Endocrine and molecular regulation mechanisms of follicular development and egg-laying in quails under different photoperiods

Photoperiod is a key environmental factor in regulating bird reproduction and induces neuroendocrine changes through the hypothalamic-pituitary-gonadal (HPG) axis. OPN5, as a deep-brain photoreceptor, transmits light signals to regulate follicular development through TSH-DIO2/DIO3. However, the mechanism among OPN5, TSH-DIO2/DIO3, and VIP/PRL in the HPG axis underlying the photoperiodic regulation of bird reproduction is unclear. In this study, 72 laying quails with 8-week-old were randomly divided into the long-day (LD) group [16 light (L): 8 dark (D)] and the short-day (SD) group (8 L:16 D), and then samples were collected on d 1, d 11, d 22, and d 36 of the experiment. The results showed that compared with the LD group, the SD group significantly inhibited follicular development (P < 0.05), decreased the P4, E2, LH, and PRL in serum (P < 0.05), downregulated the expression of GnRHR, VIP, PRL, OPN5, DIO2, and LHβ (P < 0.05), reduced the expression of GnRH and TSHβ (P > 0.05), and promoted DIO3, GnIH gene expression (P < 0.01). The short photoperiod downregulates OPN5, TSHβ, and DIO2 and upregulates DIO3 expression to regulate the GnRH/GnIH system. The downregulation of GnRHR and upregulation of GnIH resulted in a decrease in LH secretion, which withdrew the gonadotropic effects on ovarian follicles development. Slow down of follicular development and egg laying may also arise from lack of PRL potentiation to small follicle development under short days.

Impact of COVID-19 vaccination on menstruation pattern among female nursing and paramedical students in a peripheral medical college in Eastern India

Background: Many females worldwide have reported abnormalities in their menstrual patterns post-COVID-19 vaccination. The present study was conducted to determine the impact of the COVID-19 vaccination on menstrual patterns among female nursing and paramedical students at a peripheral medical college in eastern India. Materials and Methods: The cross-sectional, online self-administered survey was conducted using Microsoft Forms after taking institutional ethical clearance and informed consent from the participants. Two hundred BSc nursing and paramedical students who had received two doses of COVID vaccination (Covaxin or Covishield) and were not suffering from any endocrinopathies, bleeding disorders, structural gynecological abnormalities, or taking any medication known to affect the hypothalamic–pituitary–gonadal axis were included in the study. The questionnaire included menstrual length cycle length and amount of bleeding and there were no direct identifiers. Results: The participants reported a significant increase in the amount of bleeding on the heaviest day (mean ± standard deviation [SD] of the number of pads used was 3.52 ± 1.15 during prevaccination months vs. 4.64 ± 1.36 during postvaccination months; P &lt; 0.001) following vaccination. A similar result of increased bleeding on the heaviest day of the period was obtained in both the Covaxin group (mean ± SD: 3.08 ± 1.16 vs. 4.88 ± 1.53; P: 0.001) and the Covishield group (mean ± SD: 3.59 ± 1.13 vs. 4.6 ± 1.34; P &lt; 0.001). No difference in change in the menstrual pattern was observed between the two groups who had received two different types of vaccine (P: 0.527). Conclusion: The study showed a possible connection between the COVID-19 vaccination and the change in menstrual patterns.

Overview of the Effects of Moringa oleifera Leaf Extract on Oxidative Stress and Male Infertility: A Review

According to a recent report by the WHO, 50–80 million people suffer with infertility. Amongst these populations, male counterparts account for 20–50% of infertility cases. The aetiology of infertility in men includes many factors such as psychological issues, lifestyle and environmental factors, hormonal disorders and chromosomal abnormalities. The pathophysiology of these aetiologies may be initiated by a local inflammatory reaction increasing reactive oxygen species (ROS) production, which can negatively affect the male reproductive system by altering the hypothalamic–pituitary–gonadotropin axis (HPG axis). Alteration of the HPG axis may affect testicular steroidogenesis, spermatogenesis, the Leydig cells and Sertoli cells, leading to poor semen quality. The prevalence of male infertility underscores the need for a thorough scientific investigation to identify treatable or reversible factors using plant adjuvants with antioxidative properties. Therefore, this review aims to provide an overview of the currently available knowledge on the aetiologies of male reproductive dysfunction, emphasising infertility risk factors, as well as elucidating the possible ways by which readily available alternatives, such as Moringa oleifera leaves, may mitigate male infertility by highlighting its role on the oxidative stress parameters, reproductive hormonal levels, testicular steroidogenesis and spermatogenesis, gene expression, weight and morphology of the testis and sperm parameters.

Neuroendocrine pathogenesis of perimenopausal depression.

With the development of social economics and the increase of working pressure, more and more women are suffering from long-term serious stress and showing symptoms of perimenopausal depression (PMD). The incidence rate of PMD is increasing, and the physical and mental health are seriously affected. However, due to the lack of accurate knowledge of pathophysiology, its diagnosis and treatment cannot be accurately executed. By consulting the relevant literature in recent years, this paper elaborates the neuroendocrine mechanism of perimenopausal depression from the aspects of epigenetic changes, monoamine neurotransmitter and receptor hypothesis, glial cell-induced neuroinflammation, estrogen receptor, interaction between HPA axis and HPG axis, and micro-organism-brain gut axis. The purpose is to probe into new ways of treatment of PMD by providing new knowledge about the neuroendocrine mechanism and treatment of PMD.

Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is an autoimmune disease affecting the CNS and occurring far more prevalently in women than in men. In both MS and its animal models, sex hormones play important immunomodulatory roles. We have previously shown that experimental autoimmune encephalomyelitis (EAE) affects the hypothalamic-pituitary-gonadal axis in rats of both sexes and induces an arrest in the estrous cycle in females. To investigate the gonadal status in female rats with EAE, we explored ovarian morphometric parameters, circulating and intraovarian sex steroid levels, and the expression of steroidogenic machinery components in the ovarian tissue. A prolonged state of diestrus was recorded during the peak of EAE, with maintenance of the corpora lutea, elevated intraovarian progesterone levels, and increased gene and protein expression of StAR, similar to the state of pseudopregnancy. The decrease in CYP17A1 protein expression was followed by a decrease in ovarian testosterone and estradiol levels. On the contrary, serum testosterone levels were slightly increased. With unchanged serum estradiol levels, these results point at extra-gonadal sites of sex steroid biosynthesis and catabolism as important regulators of their circulating levels. Our study suggests alterations in the function of the female reproductive system during central autoimmunity and highlights the bidirectional relationships between hormonal status and EAE.

Discover boy specific-biomarkers and reveal gender-related metabolic differences in central precocious puberty

The incidence of central precocious puberty (CPP) in boys is rising, but lack of effective molecular biomarkers often leads to delayed treatment and thus the terrible clinical complications in adulthood. This study aims to identify the specific-biomarkers of CPP boys and understand the gender-related differences in metabolic characteristics of CPP. The specific-biomarkers of CPP boys were identified from serum by cross-metabolomics combined with linear discriminant analysis effect size analysis after age correction, and union receiver operating characteristic curve analyses were perform to optimize the combination of specific-biomarkers. The differences in metabolic characteristics between boys and girls with CPP were explored by cross-metabolomics and weighted gene co-expression network analysis. Results show that CPP activated in advance the HPG axis and induced gender-related clinical phenotypes. Seven serum metabolites were identified as specific-biomarkers of CPP boys, including acetoacetate, aspartate, choline, creatinine, myo-inositol, N,N-dimethylglycine and N-Acetyl-glycoprotein. The combination of aspartate, choline, myo-inositol and creatinine achieved an optimized diagnosis, where AUC is 0.949, prediction accuracy for CPP boys is 91.1%, and the average accuracy is 0.865. The metabolic disorders of CPP boys mainly involve in glycerophospholipid metabolism, and synthesis and degradation of ketone bodies. Betaine, glutamine, isoleucine, lactate, leucine, lysine, pyruvate, α-&β-glucose were identified as gender-related biomarkers for CPP, and they are mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. Biomarkers combination provides a promising diagnostic potential for CPP boy with a favorite sensitivity and specificity. In addition, the differences of metabolic characteristics between boys and girls with CPP will contribute to the development of individualized clinical treatments in CPP.

Frequency-dependent alterations in regional homogeneity associated with puberty hormones in girls with central precocious puberty: A resting-state fMRI study

ObjectiveCentral precocious puberty (CPP) patients are at significantly higher risk of emotional, mental, and behavioral disorders than those normal pubertal population. However, to date, the definite mechanism of how puberty hormones affect patients with CPP remains unclear. This regional homogeneity (ReHo) study aimed to explore the impact of premature hypothalamus-pituitary-gonadal (HPG) axis activation on brain function alteration in girls with CPP, meanwhile, to explore the relationship between gonadotropin and gonadal hormones levels, abnormal brain activity and cognitive function. MethodsIn this prospective study, a total of 85 girls who were suspected of having CPP were enrolled from the Child Healthcare Department of the Second Affiliated Hospital of Wenzhou Medical University Hospital from June 2018 to May 2021, including 41 CPP girls and 44 non-CPP girls. All participants collected the 0, 30, 60 min blood luteinizing hormone (LH), follicle-stimulating hormone (FSH), 0, 30 min estradiol (E2) and baseline cortisol (COR) and prolactin (PRL) concentrations after gonadotrophin-releasing hormone (GnRH) stimulating test. Resting-state magnetic resonance imaging (rs-MRI) scans were performed for all participants at 2 weeks before the GnRH stimulating test, voxel-wise ReHo was calculated in the standard frequency band (0.01–0.10 Hz), and in slow-4 (0.027–0.073 Hz) and slow-5 (0.01–0.027 Hz). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) was also collected. Independent-sample t-test or Mann-Whitney U test was used to compare the differences between two groups. The correlation analysis among abnormal brain regions, serum hormone levels and WISC-IV scores were performed by Spearman or partial correlation analysis. ResultsCompared to the non-CPP group, the CPP group showed higher regional homogeneity (ReHo) values in the left inferior temporal gyrus (ITG.L), as well as lower ReHo values in left superior temporal gyrus (STG.L), left superior occipital gyrus (SOG.L) and the right middle gyrus (MTG.R) in slow4.in slow5 frequency band, CPP group demonstrated decreased ReHo values in bilateral orbital part of superior frontal gyrus and medial superior frontal gyrus. LimitationDue to the cross-section design of this study, further research is needed to explore the relationships between age, premature activation HPG axis and brain function changes. ConclusionOur findings demonstrate that premature HPG axis activation and alterations in puberty hormones, may lead to changes in brain activity and cognitive function. This rs-fMRI study may enhance our understanding of the neuroendocrine mechanisms of mood, behavior, and cognitive function alterations in patients with CPP.

Timosaponin AIII attenuates precocious puberty in mice through downregulating the hypothalamic-pituitary-gonadal axis.

Precocious puberty (PP) has increasingly become a social concern. This study aimed to investigate the effect of timosaponin AIII (TAIII) on the precocious puberty and its possible mechanisms in mice. Four groups of mice consisting of controls that received saline or TAIII, a model that received leptin to induce precocious puberty (PP), and leptin+TAIII (the leptin model treated with TAIII) were used to determine the effect of TAIII on PP. Pathological and cytological examinations were conducted to investigate the signs and onset of PP and the development of reproductive organs. The level of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were determined using enzyme-linked immunosorbent assay (ELISA). The expression of genes related to the hypothalamic-pituitary-gonadal axis (HPGA) was assessed using qRT-PCR and Western blotting. Bone mineral density (BMD) was determined using high resolution peripheral quantitative computed tomography. In mice treated with leptin, earlier vaginal opening and estrus were observed, as well as the increased ovarian and uterine weight, total uterine cross-sectional size, number of corpora lutea, and elevated serum sex hormone levels and HPGA expression. On the other hand, TAIII treatment delayed the vaginal opening and vaginal estrus to 32.1 and 37.5 days after birth, and delayed the development of reproductive organs, leading to significantly smaller uterus and ovary size, less corpora lutea and low BMD (P<0.05). In addition, the serum levels of LH, FSH and E2 were significantly reduced (P<0.05) and so was the expression of HPGA and leptin genes (P<0.05). Our experimental data demonstrated that TAIII has activity against leptin-induced PP activity and may attenuate PP by reducing reproductive hormones and deactivating the hypothalamic-pituitary-gonadal axis through downregulating leptin expression.

SARS-CoV-2 and male infertility: from short- to long-term impacts.

The coronavirus 2019 (COVID-19) pandemic-caused by a new type of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-has posed severe impacts on public health worldwide and has resulted in a total of >6 million deaths. Notably, male patients developed more complications and had mortality rates ~77% higher than those of female patients. The extensive expression of the SARS-CoV-2 receptor and related proteins in the male reproductive tract and the association of serum testosterone levels with viral entry and infection have brought attention to COVID-19's effects on male fertility. The peer-reviewed articles and reviews were obtained by searching for the keywords SARS-CoV-2, COVID-19, endocrine, spermatogenesis, epididymis, prostate, and vaccine in the databases of PubMed, Web of Science and Google Scholar from 2020-2022. This review summarizes the effects of COVID-19 on the male reproductive system and investigates the impact of various types of SARS-CoV-2 vaccines on male reproductive health. We also present the underlying mechanisms by which SARS-CoV-2 affects male reproduction and discuss the potentially harmful effects of asymptomatic infections, as well as the long-term impact of COVID-19 on male reproductive health. COVID-19 disrupted the HPG axis, which had negative impacts on spermatogenesis and the epididymis, albeit further investigations need to be performed. The development of vaccines against various SARS-CoV-2 variations is important to lower infection rates and long-term COVID risks.

Genital epithelial barrier function is conserved by intravaginal rings releasing etonogestrel and ethinyl estradiol

ABSTRACT The injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract.