Serum Luteinizing Hormone Concentrations Research Articles

Exploring the potential of selenium nanoparticles and fabricated selenium nanoparticles @vitamin C nanocomposite in mitigating nicotine-induced testicular toxicity in rats.

The tobacco epidemic signifies a major public health threat. Nicotine (NIC), a major active constituent in tobacco, impedes male fertility and semen quality. This work is implemented to explore the potential of selenium nanoparticles (SeNPs) and the newly fabricated SeNPs @vitamin C (SeNPs@VITC) nanocomposite in mitigating testicular toxicity induced by NIC. The six groups of 48 adult Wistar rats were designed as follows: the control group injected intraperitoneally with normal saline, the SeNPs group treated orally with 2mg/kg of SeNPs, the SeNPs@VITC nanocomposite group treated orally with 2mg/kg of SeNPs@VITC nanocomposite, the NIC group injected intraperitoneally with 1.25mL/kg of NIC, the NIC+ SeNPs group received SeNPs plus NIC, and the NIC+ SeNPs@VITC nanocomposite group received SeNPs@VITC nanocomposite plus NIC. Treatments were administered over a 28-day period. NIC treatment significantly caused poor sperm quality, decreased serum testosterone, increased follicle-stimulating hormone (FSH), luteinizing hormone (LH) concentrations, reduced hemoglobin levels, leukocytosis, disrupted testicular oxidant/antioxidant balance, and disorganized testicular structure. The construction of the novel SeNPs@VITC nanocomposite, compared to NIC plus SeNPs alone, demonstrated a more potent ameliorative effect on NIC-induced reproductive toxicity in adult rats. The SeNPs@VITC nanocomposite significantly increased sperm count, reduced the percentage of sperm head abnormalities, lowered both serum FSH and LH concentrations, and improved the hemoglobin response. Both SeNPs and SeNPs@VITC nanocomposite alleviated the testicular toxicity induced by NIC, but the SeNPs@VITC nanocomposite exhibited superior efficacy. The SeNPs@VITC nanocomposite could be employed to advance enhanced therapeutic strategies for addressing male infertility.

EFFECT OF HEAT STRESS ON PRODUCTION PERFORMANCE IN DAIRY ANIMALS

The high-temperature stress and combination of high temperature and humidity during summer months in Punjab is an important factor for dairy cows as it directly affects the daily milk yield of dairy cows. The research was conducted on to effect of high-temperature stress on different parameters associated with daily milk yield. For this purpose, 5 freshly parturated Sahiwal breeds of dairy cows were to evaluate the effect of temperature humidity index on Daily milk yield at different temperature humidity index levels i.e. comfortable (≤ 70), mild stress (71–80), moderate stress (81–90), and stressful (≥90) zone. Blood samples were collected and centrifuged to get serum and ELISA was accomplished by using a spectrometer. Results revealed high significant (P < 0.001) increment in cortisol and triglycerides concentration and high significant reduction in serum progesterone (P < 0.001) and Luteinizing hormone (P < 0.001) concentration in cows during stressful environments. Daily milk yield has significant (P < 0.05) variation and a decreasing trend in cows from comfortable to stressful conditions. Progesterone and LH had a highly significant positive correlation with daily milk yield. Cortisol and triglycerides had a non-significant negative correlation with daily milk yield. It is concluded that heat stress has a negative impact on the daily milk yield as it disturbs the hormonal balance of the animal.

Preparation of oyster peptide and Pfaffia glomerata pressed candy and its ameliorative effect on sexual dysfunction in male mice.

Oyster peptide (OP) and Pfaffia glomerata extract (PGE) were used as raw materials. The optimal formulation of the pressed candy (PC) was optimized by one-way experiment and D-optimal mixture experiment design, and animal experiment was used to evaluate the effect of PC on male sexual dysfunction. The results showed that PC intervention significantly improved the sexual behavior of male mice with sexual dysfunction, including a significant shortening of the mount latency (ML) and intromission latency, and a significant increase in the mount frequency (MF) and intromission frequency (IF). At the same time, the concentrations of serum testosterone (T) and luteinizing hormone (LH) in mice were restored, and the erectile parameters and pathological changes of penile tissue were improved. Further studies found that PC intervention increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the content of malondialdehyde (MDA) in testicular tissue. In addition, PC intervention improved testicular tissue morphology. In conclusion, the obtained PC has good taste quality, and the relevant quality indicators are qualified. It has a good ameliorative effect on male sexual dysfunction and may be a potential dietary supplement.

The opioid peptide leucine enkephalin modulates hypothalamic-hypophysial axis in the cichlid fish Oreochromis mossambicus

In vertebrates, opioid peptides are thought to be involved in the regulation of reproduction; however, the significance of enkephalins in testicular function remains unclear. We examined the influence of δ-opioid receptor agonist leucine enkephalin (L-ENK) on the hypophysial-testicular axis of the cichlid fish Oreochromis mossambicus. Treatment with a low dose of L-ENK (60 µg) caused a significant increase in the numbers of primary and secondary spermatocytes and early and late spermatids, concomitant with intense immunolabelling of testicular androgen receptors, but did not significantly alter serum luteinizing hormone (LH) and 11-ketotestosterone (11-KT) levels compared to those of controls. Nevertheless, treatment with a high dose of L-ENK (200 µg) caused a significant reduction in the numbers of secondary spermatocytes as well as late spermatids associated with marginal immunolabelling of androgen receptors and significantly lower concentrations of serum 11-KT and LH compared to controls. In addition, the serum cortisol level was not affected in low-dose L-ENK-treated fish, but its level was significantly increased in the high-dose L-ENK-treated group. Together, these findings indicate that a low dose of L-ENK stimulates the germ cells at the meiosis stage and promotes further stages of spermatogenesis, whereas a high concentration of L-ENK inhibits spermatogenesis at the advanced stages. This effect appears to be mediated through the suppression of testicular steroidogenesis and the reduction of LH release in the pituitary gland of tilapia. The findings also suggest that elevated L-ENK levels in teleosts may exert their inhibitory influence on the hypophysial-testicular axis via glucocorticoids.

Peak serum luteinising hormone cut-off during gonadotropin-releasing hormone analogue test for diagnosing central precocious puberty was lower in girls with obesity as compared with girls with normal weight.

Serum luteinising hormone (LH) concentration has been reported to be lower in girls with overweight and obesity (OW/OB) as compared with girls with normal weight (NW). This study aimed to evaluate peak serum LH concentration during gonadotropin-releasing hormone analogue (GnRHa) test in girls with OW/OB and NW who had central precocious puberty (CPP) and to determine peak serum LH cut-off for diagnosing CPP in girls with OW/OB. Medical records of 971 girls with premature breast development who underwent subcutaneous GnRHa (100 µgof triptorelin acetate) test were reviewed. All girls were classified as either CPP or premature thelarche. All of them were further classified into two groups according to their body mass index as NW and OW/OB groups for each Tanner stage. There were 634 and 337 girls in NW and OW/OB groups, respectively. CPP was diagnosed in 600 girls (249 had Tanner stage II and 351 had Tanner stage III). There were no differences in peak serum LH concentrations between CPP girls with NW and OW/OB. Peak serum LH cut-off of 5 IU/L (the current widely used cut-off) had a sensitivity and a specificity of 75% and 90%, respectively in NW group. Peak serum LH cut-off for CPP diagnosis was lower at 4 IU/L in the OW/OB group with greater sensitivity and specificity of 86% and 93%, respectively. The results were reproducible for each Tanner stage of breasts. Lower peak serum LH cut-off to 4 IU/L for diagnosing CPP in girls with OW/OB should be considered to avoid underdiagnosis of the condition.

Therapeutic effects of melatonin in female mice with central precocious puberty by regulating the hypothalamic Kiss-1/Kiss1R system

In recent years, central precocious puberty (CPP) in children is becoming more common, which seriously affects their physical and psychological health and requires finding a safe and effective treatment method. The aim of this study was to investigate the therapeutic effect of melatonin on CPP. A CPP model was established by subcutaneous injection of 300 micrograms of danazol into 5-day-old female mice, followed by treatment with melatonin and leuprolide. The vaginal opening was checked daily. Mice were weighed, gonads were weighed, gonadal index was calculated, and gonadal development was observed by hematoxylin and eosin (HE) staining. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels were measured by ELISA. By using RT-PCR and Western blotting, the mRNA and protein expression of the hypothalamus Kiss-1, Kiss-1 receptor (Kiss1R), gonadotropin-releasing hormone (GnRH), and pituitary GnRH receptor (GnRHR) were identified. The results showed that melatonin delayed vaginal opening time and reduced body weight, gonadal weight and indices in female CPP mice. Melatonin treatment prevents uterine wall thickening and ovarian luteinization in female CPP mice. Melatonin treatment reduces serum concentrations of FSH, LH, and E2 in female CPP mice. Melatonin suppressed the expressions of Kiss-1, Kiss1R and GnRH in the hypothalamus, and the expression of GnRHR in the pituitary of the female CPP mice. Our results suggest that melatonin can inhibit the hypothalamic-pituitary-gonadal (HPG) axis by down-regulating the Kiss-1/Kiss1R system, thereby treating CPP in female mice.

294 KISS1 Knockout Boars Have Decreased Concentrations of Gonadotropins Leading to Smaller Testes and Reduced Skatole in Backfat

Abstract In swine production, boars are castrated to prevent boar taint from testicular androgens and skatole accumulation in fat. Kisspeptin (KISS1) regulates secretion of gonadotropins and gonadal steroids. We used boars from our line of KISS1-/-pigs (10.3389/fgene.2022.1078991) to understand how loss of KISS1 function affects compounds causing boar taint. Boars were fed ad libitum during development. Body weights and testicular volume (TV) were collected at weaning, 40, 70, 100, 130, 160, and 190 d of age using TV = 4/3*π *a*b2*2 and subtracting scrotal skin thickness measured by a Harpenden skinfold caliper. Average daily gain (ADG) was calculated by subtracting the beginning from ending body weight at each age range and dividing by the number of days. At each age, a blood serum sample was collected by jugular venipuncture to quantify changes in hormones during development. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were quantified with radioimmunoassay and analyzed as repeated measures with genotype (KISS1+/+; KISS1+/-; KISS1-/-; n = 8 – 20 animals per genotype) and age as the fixed effects. Concentrations of androstenone and skatole in backfat (quantified using ELISA and HPLC, respectively) were log transformed and analyzed with ANOVA. Body weight did not differ among KISS1 genotypes but increased normally with age (P < 0.0001). During development, KISS1+/+ and KISS1+/- boars grew at similar rates. Although the ADG of KISS1-/-boars was similar to other genotypes up to 160 d of age, ADG was reduced at 190 d of age (age x genotype; P < 0.05). Mean concentrations of LH and FSH in KISS1+/+ and KISS1+/- boars were similar throughout development (LH, 1.16 ±0.11 and 1.34 ± 0.17 ng/mL; FSH, 0.88 ± 0.06 and 0.89 ± 0.05 ng/mL, respectively), and were greater than KISS1-/- boars (LH, 0.38 ± 0.23 ng/mL; FSH, 0.56 ± 0.07 ng/mL; P < 0.05). TV of KISS1+/+ and KISS1+/- boars did not differ during development and was greater than KISS1-/- boars (P < 0.05), for which testes could not be palpated after 100 d of age. Testosterone concentrations in KISS1+/+ and KISS1+/- increased 40-fold during development but were below detectable limits in KISS1-/- boars (age x genotype; P = 0.06). Androstenone and skatole in KISS1-/- boars (0.30 ± 1.24 µg/g and 12.6 ± 1.6 ng/g, respectively) at 190 d of age was less (P < 0.0001) than in KISS1+/+ and KISS1+/- boars (androstenone, 4.33 ± 1.16 µg/g; skatole, 69.2 ± 1.2 ng/g), which did not differ from one another. Thus, a single functional allele of KISS1 is sufficient to confer normal secretion of reproductive hormones, testicular growth, and skatole in boars. Moreover, knocking out the KISS1 gene will prevent boar taint, but might slightly reduce growth in later stages of development.

Effect of Spirulina platensis Supplementation on Reproductive Parameters of Sahrawi and Jabbali Goat Bucks.

Spirulina platensis (SP) is a protein-rich dietary supplement that improves animal reproductive traits. This study investigated the effect of SP supplementation on puberty onset, semen characteristics, scrotal circumference (SC), libido, and hormone concentrations in Sahrawi and Jabbali bucks. The study was conducted in 36 bucks, divided into three groups (n = 6/group), for 70 days. The rations included the following: (1) Control feed (Con) with 14% crude protein and 11.97% MJ/kg DM energy; (2) Con with 2 g SP/head/day SP treatment (T1) and (3) Con with 4 g SP/head/day treatment (T2). The mean (±SEM) SC of both SP groups in the Sahrawi breed was significantly higher (p ≤ 0.05) compared to the Con. The mean of the semen volume significantly increased (p ≤ 0.05) in the SP group than in the Con group in both breeds. SP groups vs. Con groups had increased sperm concentration in Sahrawi bucks than Jabbali bucks. Mean serum luteinizing hormone (LH) and testosterone (Tes) concentrations in Jabbali bucks were significantly higher (p ≤ 0.05) in the SP groups compared to Sahrawi bucks. SP improved the SC, semen quality, libido, sperm concentration, and LH and Tes concentrations in both breeds. The results of the current study suggest that adding SP to the diet may have the ability to improve the semen quality of the local Omani bucks.

PSI-A-9 A Comparison in Vaginal Gene Expression and Circulating Hormone Concentration in Pre-Pubertal Gilts Achieving Puberty at Different Ages

Abstract A known predictor of reproductive success in swine breeding herds is age at puberty. Early puberty is associated with improved long-term reproductive performance and more high-quality offspring. The objective of this study was to compare vaginal gene expression in gilts that achieved estrus early (160 to 181 d of age), average (181 to 202 d of age), late (202 to 215 d of age) and anestrus. Pre-pubertal gilts (n = 13) were followed from 70 d of age until first estrus or 214 ± 1 d. Vaginal epithelia was collected using a swabbing method at five time points during reproductive development [70 (on-farm arrival), 100 (mid-folliculogenesis), 130, 160 (start of boar exposure) d of age and standing estrus or end of trial]. At 140 d of age, females received an indwelling titanium catheter for daily blood collection during boar exposure. Following detected standing estrus, a blood sample was collected every 2 hours for 96 hours to characterize the peak serum concentration of luteinizing hormone that occurs at ovulation. At the conclusion of the trial, 3 gilts displayed early estrus (169 to 171 d of age), 3 gilts were deemed average estrus (194 to 195 d of age), 3 gilts were deemed late estrus (203 to 213 d of age), 3 gilts were deemed anestrus and 1 was identified as having a ‘silent’ estrus after 200 d of age. Total RNA were isolated from vaginal epithelia and relative gene expression insulin-like growth factor-1 (IGF-1), and estrogen receptor (ER)-alpha was quantified by real time RT-PCR, relative to the expression of RPLP0. to D70 was preformed using the PCR package offered in RStudio (version 1.2.5025). There was an increase in ER-alpha expression in the average estrus group (P = 0.03) at 130 d of age. Early estrus females had a greater expression of IGF-1 at 130 d of age compared with anestrus females (P = 0.01). Of the 9 females placed with an indwelling catheter, 2 catheters were nonpatent, and blood sample could not be collected at standing estrus. Of the 7 females where blood sample was collected at standing estrus, all females achieved an luteinizing hormone (LH) peak within 12 h after recorded standing estrus. Identification of key differences in the vaginal epithelium in concert with LH values provides biological evidence that those deemed achieving estrus based on behavior did successfully achieve estrus. These vaginal epithelium differences may serve as putative biomarkers to detect early estrus in pre-pubertal gilts.

The protective effect of hydroalcoholic extract of Ephedra pachyclada leaves on ovarian damage induced by cyclophosphamide in rat: An experimental study.

Cyclophosphamide (CP) is an anticancer drug that acts as an alkylation agent after metabolism in the liver. CP has toxic effects on the body's cells, especially the reproductive system's function, and causes infertility. Moreover, medicinal plants have few side effects and are psychologically acceptable to patients. This study aimed to investigate the impact of Ephedra pachyclada hydroalcoholic extract (EPHE) on ovarian tissue and hypothalamic-pituitary-gonadal axis in rats treated with CP. In this experimental study, 48 adult female Wistar rats (180-200 gr, 9-10 wk) were randomly assigned to 6 experimental groups (n = 8/each): (a) control; (b) sham; (c) CP; (d) CP+250 mg/kg EPHE; (e) CP+500 mg/kg EPHE; (f) CP+1000 mg/kg EPHE. On the 29 day of the experiment, serum was collected; serum concentration of the luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and antioxidant activity were measured. The number of ovarian follicles were also counted. In the CP groups, serum concentrations of follicle-stimulating hormone and luteinizing hormone significantly increased, and estrogen and progesterone significantly decreased (p 0.05). EPHE significantly compensated for the complications caused by CP and 1000 mg/kg had the greatest effect. Antioxidant reduction by CP was significantly enhanced by EPHE, especially at higher doses (p 0.05). The number of primordial, primary, secondary, and Graafian follicles showed a significant decrease in CP groups and EPHE groups showed a significant increase compared to the CP. EPHE showed that the concentration of 1000 mg/kg was more effective than other doses (p 0.05). In addition to proving the effect of EPHE on the hypothalamic-pituitary-gonadal axis, our investigation showed antioxidant properties, which can be an effective factor in CP-treated rats.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: ‘neutral’ (n = 228) with normal sex hormone homeostasis, ‘testicle’ (n = 91) with elevated T and E2, low pituitary hormones, and finally ‘pituitary’ subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Resveratrol ameliorates bisphenol A-induced testicular toxicity in adult male rats: a stereological and functional study

BackgroundBisphenol A (BPA) is one of the most widely used synthetic chemicals worldwide. BPA as an endocrine disruptor affects the reproductive systems through estrogenic and antiandrogenic proprieties. Resveratrol (RES) as a natural polyphenol and potent antioxidant exhibits protective effects against reproductive toxicity by inhibiting of oxidative stress. 48 male rats were divided into eight groups (n=6), including CONTROL, OLIVE OIL (0.5 ml/ day), Carboxy methylcellulose (CMC) (1 ml of 10 g/l), RES (100mg/kg/day), low dose of BPA (25 mg/kg/day), high dose of BPA (50 mg/kg/day), low dose of BPA + RES, and high dose of BPA + RES. All treatments were done orally per day for 56 days. At the end of the 8th week, blood samples were collected for hormone assays. Then, the sperm parameters were analyzed, and the left testis was removed for stereological study.ResultsWe showed a significant decrease in sperm parameters in the low and high doses of BPA groups compared to control groups (P<0.05). The volume of testicular components as well as the diameter and length of seminiferous tubules significantly reduced (11-64 %), and the total number of the testicular cell types decreased (34-67 %) on average in the low and high doses of BPA groups. Moreover, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone hormones concentration showed a significant reduction in both doses of BPA groups (P<0.01). Nonetheless, treatment with RES could ameliorate all the above-mentioned changes in the low and high doses of BPA groups (P<0.05).ConclusionsRES could prevent BPA-induced testicular structural changes and sperm quality via improving gonadotropin hormones and testosterone levels.

Assessment of serum fetuin-A and its gene polymorphism as a marker of insulin resistance in polycystic ovary syndrome

Background/aim Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition affecting 5–10% of reproductive-aged women, the cause of which is unknown. Chronic anovulation, polycystic ovaries, and hyperandrogenism are symptoms of PCOS. It is linked to hirsutism, obesity, and increased probability of cardiovascular disease, metabolic syndrome, and diabetes mellitus. A risk factor for cardiovascular disease is PCOS that is undiagnosed or untreated. Our aim in this study is to investigate serum fetuin-A level and its gene as potential biomarkers for screening of insulin resistance in PCOS. Patients and methods This study involved 100 female participants from outpatient clinic, Department of Obstetrics and Gynecology, Zagazig University Hospital, Egypt. They were split into two groups (each 50). The first group included healthy fertile women without symptoms of hyperandrogenemia as a control. The second group included women with PCOS. Fasting blood sugar levels, cholesterol, high-density lipoprotein cholesterol and triglycerides have been estimated by enzymatic colorimetric technique while low-density lipoprotein cholesterol was calculated. Enzyme-linked immunosorbent assays have been used to measure serum concentrations of luteinizing hormone, follicular-stimulating hormone, testosterone, and fetuin-A, while PCR has been used to extract DNA and genotype common functional polymorphisms in fetuin-A. Results The present results revealed a considerable rise in glucose, insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), cholesterol, triglyceride, low-density lipoprotein cholesterol, luteinizing hormone, testosterone, and fetuin-A and significant decrease in follicular-stimulating hormone and high-density lipoprotein cholesterol in PCOS patients. Also, there was significant higher frequency of the fetuin-A gene variant rs1071592 AA genotype and A allele compared to controls. Conclusions Fetuin-A has a potential diagnostic value as a biomarker for insulin resistance in PCOS associated with metabolic syndrome. Additionally, ‘CG’ allele can be considered a risk factor for PCOS.

Aging and androgens: Physiology and clinical implications.

In men > ~35years, aging is associated with perturbations in the hypothalamus-pituitary-testicular axis and declining serum testosterone concentrations. The major changes are decreased gonadotropin-releasing hormone (GnRH) outflow and decreased Leydig cell responsivity to stimulation by luteinizing hormone (LH). These physiologic changes increase the prevalence of biochemical secondary hypogonadism-a low serum testosterone concentration without an elevated serum LH concentration. Obesity, medications such as opioids or corticosteroids, and systemic disease further reduce GnRH and LH secretion and might result in biochemical or clinical secondary hypogonadism. Biochemical secondary hypogonadism related to aging often remits with weight reduction and avoidance or treatment of other factors that suppress GnRH and LH secretion. Starting at age ~65-70, progressive Leydig cell dysfunction increases the prevalence of biochemical primary hypogonadism-a low serum testosterone concentration with an elevated serum LH concentration. Unlike biochemical secondary hypogonadism in older men, biochemical primary hypogonadism is generally irreversible. The evaluation of low serum testosterone concentrations in older men requires a careful assessment for symptoms, signs and causes of male hypogonadism. In older men with a body mass index (BMI) ≥ 30, biochemical secondary hypogonadism and without an identifiable cause of hypothalamus or pituitary pathology, weight reduction and improvement of overall health might reverse biochemical hypogonadism. For older men with biochemical primary hypogonadism, testosterone replacement therapy might be beneficial. Because aging is associated with decreased metabolism of testosterone and increased tissue-specific androgen sensitivity, lower dosages of testosterone replacement therapy are often effective and safer in older men.

Relationship between GnRH-induced LH increase profiles in the serum and vaginal mucus of Japanese Black beef cows.

This study aimed to investigate the relationship between increases in the luteinizing hormone (LH) profiles in the serum and vaginal mucus of cows induced by gonadotropin-releasing hormone (GnRH). Samples for LH determination were collected from Japanese Black beef cows during estrus, which was induced with a controlled internal progesterone-releasing device and the administration of cloprostenol immediately before GnRH administration and every 30 min from the start of GnRH administration until 6.5 h. The peak serum LH concentration was clearly identified at 2.5 h post-GnRH administration, with serum concentrations returning to near-pre-GnRH-administration values after 6.5 h, whereas the peak vaginal mucus LH concentration was identified 4.5 h after GnRH administration. These results indicate that the LH secretion peak in vaginal mucus appeared about 2 h after peak LH secretion in the serum.

Nesfatin-1 as a potential marker for functional hypothalamic amenorrhea

Objective Nesfatin-1 plays an important role in regulating metabolism, appetite, gut motility, and eating behavior. It is suspected that abnormalities in nesfatin-1 secretion may be involved in the development of anorexia nervosa, and as such, this study aims to investigate the “circumstances of” nesfatin-1 in patients with functional hypothalamic amenorrhea (FHA). Materials and Methods One hundred and forty-seven patients with FHA were enrolled to the present study. A control group consisting of 88 healthy, age-matched subjects was used. Both study and control groups had blood samples drawn to establish baseline serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol, prolactin, thyroid-stimulating hormone, fT4, morning cortisol, dehydroepiandrosterone sulfate, testosterone, glucose, and insulin. Nesfatin-1 was also measured with the use of enzyme-linked immunosorbent assay. Results Patients with FHA were found to have a significantly decreased concentration of serum nesfatin-1 when compared to healthy controls (6.21 ± 4.79 vs. 8.64 ± 6.63 respectively, p = 0.005). No statistically significant difference in nesfatin-1 levels was found between patients with normal and decreased BMI in the FHA group. Significant positive correlation was observed between serum nesfatin-1 concentration and 17-β-estradiol, while a significant negative correlation was observed between serum nesfatin-1 concentration and patient age, fasting glucose, and HDL levels. Conclusions This is the first known study to examine nesfatin-1 concentration in the context of clinical FHA. Patients with FHA were found to have decreased serum nesfatin-1 concentrations. This finding may prove instrumental in our future approach managing patients with FHA.

Pharmacological characterization of linzagolix, a novel, orally active, non-peptide antagonist of gonadotropin-releasing hormone receptors.

Control of gonadotropin-releasing hormone (GnRH) signalling is an effective strategy for the treatment of sex hormone-dependent diseases. GnRH analogues have been widely used for treating these diseases; however, initial stimulation or complete suppression of GnRH signalling by GnRH analogues results in the occurrence of several distinct adverse effects. Accordingly, we aimed to discover small molecule GnRH antagonists with superior pharmacokinetic and pharmacodynamic profiles. Linzagolix is a potent, orally available, and selective GnRH antagonist. Here, we reported the pharmacological characterization of linzagolix in vitro and in vivo. Linzagolix selectively binds to the GnRH receptor and inhibits GnRH-stimulated signalling, in a manner comparable to cetrorelix, a peptide GnRH antagonist. Because the inhibitory effect of the gonad axis is useful for the treatment of gynaecological conditions such as endometriosis and uterine fibroids, we investigated the effect of orally administrated linzagolix on the gonadal axis in ovariectomized and intact cynomolgus monkeys. In ovariectomized monkeys, linzagolix immediately suppressed the serum luteinizing hormone concentration at doses over 1mg/kg, indicating dose-dependent inhibition that correlated with serum linzagolix concentrations. In intact female monkeys, repeated linzagolix administration suppressed hormone surges and ceased or prolonged menstrual cycles. Furthermore, all animals presenting arrested menstrual cycles following linzagolix treatment showed recovery of hormone secretion and regular menstrual cycles after administration periods ended. Our results demonstrated that linzagolix has potential as a novel agent for reproductive-age women suffering from sex hormone-dependent diseases.

Immunocastration in adult boars as a model for late-onset hypogonadism.

BackgroundWhile immunocastration has been studied in male pre‐pubertal pigs, data on older, sexually mature animals are limited. To understand the physiological effects of androgen deprivation in the late sexual development phase, we compared mature immunocastrated boars (n = 19; average age = 480 days) to young male immunocastrated pigs (n = 6; average age = 183 days) and young entire males (n = 6; average age = 186 days) as positive and negative controls, respectively.ObjectivesWe hypothesized that the timing of gonadotropin‐releasing hormone suppression (early or late sexual development phases) influences the extent of reproductive function inhibition, histological structure of testicular tissue, and expression levels of selected genes related to steroid metabolism.Materials and methodsAntibody titer, hormonal status, and histomorphometric analysis of testicular tissue were subjected to principal component analysis followed by hierarchical clustering to evaluate the immunocastration effectiveness in mature boars.ResultsHierarchical clustering differentiated mature immunocastrated boars clustered with young immunocastrated pigs from those clustered with entire males. Although all mature immunocastrated boars responded to vaccination, as evidenced by the increased gonadotropin‐releasing hormone antibody titers (p < 0.001), decreased serum luteinizing hormone concentrations (p = 0.002), and changes in testicular tissue vascularization (lighter and less red testicular parenchyma; p ≤ 0.001), the responses were variable. Sharp decreases in testes index (p < 0.001), Leydig cell volume density (p < 0.001), Leydig cell nucleus‐to‐cytoplasm ratio (p < 0.001), and testosterone concentration (p < 0.001) were observed in mature immunocastrated boars clustered with young immunocastrated pigs compared with those that clustered with entire males. Additionally, mature immunocastrated boars clustered with young immunocastrated pigs showed lower hydroxysteroid 17‐beta dehydrogenase 7 expression than entire males (p < 0.05). The young immunocastrated pigs group showed higher follicle‐stimulating hormone receptors than the entire males and mature immunocastrated boars, lower steroidogenic acute regulatory protein expression levels compared with entire males, and mature immunocastrated boars clustered with entire males (p < 0.01).ConclusionThe two‐dose vaccination regime resulted in progressive but variable regression of testicular function in adult (post‐pubertal) pigs; however, it was insufficient to induce a complete immunocastration response in all animals.

Protective effect of mixture of honey and Garcinia kola extract against cyclophosphamide–induced reproductive toxicity in male albino rats

Cyclophosphamide is a widely used drug for the treatment of many human malignant tumors. This study evaluated the protective potentials of fresh honey and Garcinia kola extract against reproductive toxicity caused by Cyclophosphamide in male Wistar rat. Group A served as the negative control and were administered feed and normal saline (2 ml/kg bw) daily for six weeks by oral gavage. Group B served as positive control and received feed and Cyclophosphamide (100mg/kg bw) via injection after 24hrs was given normal saline for six weeks. Groups C, D and E received Cyclophosphamide (100 mg/kg bw) via injection after 24hrs was respectively administered fresh honey (2ml/kg bw), a mixture of Garcinia kola and unprocessed Honey (2 ml/kg bw) plus Garcinia kola extract (100mg/kg bw) for the next six weeks. Animals in groups C, D and E revealed increased in body weight gain and this was statistically significant at p&lt;0.05. The final body weight of the cyclophosphamide treated rats was significantly reduced from 183.2±8.02 to 195.10±8.08. A significant (P&lt;0.05) reduction in the weight of the testis of the rats administered with cyclophosphamide compared with the positive control was observed (0.93±0.050 vs 1.22±0.15). However, post treatment with fresh honey, Garcinia kola and a combination of honey and Garcinia kola significantly improved the weights of testes compared with positive control (Group C: 1.13±0.05 vs 0.93±0.05; Group D: 1.20 ±0.020 Vs 93±0.05; Group E: 1.18±0.040 vs 93±0.05). The serum concentration of Luteinizing Hormone, Follicle Stimulating Hormone and testosterone was significant (P&lt;0.05) reduced in group B rats compared with Group A rats. Separate treatments with Garcinia kola extracts and unprocessed honey cause an elevation in serum LH, FSH and testosterone levels compared with the positive control rats. The mixture of Garcinia kola extracts and fresh honey improved serum levels LH, FSH and testosterone significantly (p&lt;0.05) (Group E) compared with group B. The results obtained indicated that fresh honey and Garcinia kola either used separately or in combination can ameliorate Cyclophosphamide (CPA) induced reproductive toxicity in rats.

Sex-specific hypothalamic expression of kisspeptin, gonadotropin releasing hormone, and kisspeptin receptor in progressive demyelination model

Demyelinating diseases, such as multiple sclerosis, decrease the quality of life of patients and can affect reproduction. Assisted reproductive therapies are available, which although effective, aggravate motor symptoms. For this reason, it is important to determine how the control of the hypothalamus-pituitary-gonadal axis is affected in order to develop better strategies for these patients. One way to determine this is using animal models such as the taiep rat, which shows progressive demyelination of the central nervous system, and was used in the present study to characterize the expression of gonadotrophin-releasing hormone (GnRH), Kisspeptin, and kisspeptin receptor (Kiss1R) and luteinizing hormone (LH) secretion. The expression of kisspeptin, GnRH, and Kiss1R was determined at the hypothalamic level by immunofluorescence and serum LH levels were determined by ELISA. The expression of kisspeptin at the hypothalamic level showed sexual dimorphism, where there was an increase in males and a decrease in females during oestrus. There was no change in the expression of GnRH or kisspeptin receptor, regardless of sex. However, a decrease in serum LH concentration was observed in both sexes. The taiep rat showed changes in the expression of kisspeptin at the hypothalamic level. These changes are different from those reported in the literature with the use of animals with experimental allergic encephalomyelitis, this is because both animal models represent different degrees of progression of multiple sclerosis. Our results suggest that the effects on the hypothalamus-pituitary-gonadal axis depend on the differences between the demyelinating processes, their progression, and even individual factors, and it is thus important that fertility treatments are individualized to maximize therapeutic effects.