Gonadotropin-releasing Hormone Administration Research Articles

O-192 Kisspeptin as a test of hypothalamic function in women presenting with oligo-amenorrhea

Abstract Study question Can kisspeptin be used as a novel tool to interrogate hypothalamic function in women presenting with oligo-amenorrhea? Summary answer The hormonal response to kisspeptin offers a novel approach for the assessment of hypothalamic function in patients presenting with oligo-amenorrhea of different aetiologies. What is known already Polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhea (FHA) are the two commonest causes of anovulation causing oligo-amenorrhea in pre-menopausal women. Additionally, congenital (CHH) and functional hypogonadotropic hypogonadism can present with similar endocrine profiles. Importantly, these conditions are caused and characterised by abnormal hypothalamic function. For instance, gonadotropin-releasing hormone (GnRH) pulsatility is increased in PCOS but reduced in FHA. Despite differences in pathophysiology, differentiating these diagnoses can be challenging in clinical practice. Kisspeptin is known to stimulate hypothalamic GnRH neurons. Thus, kisspeptin could represent a novel tool to interrogate hypothalamic function in women presenting with reproductive disorders causing oligo-amenorrhea. Study design, size, duration Single-centre, prospective, experimental study of healthy women (n = 33), women with PCOS (n = 30), FHA (n = 30), or CHH (n = 8), aged 18-35 years and not taking hormonal treatment. Participants were recruited for clinical studies between September 2019 and September 2023 and underwent two separate study visits. The visits assessed the gonadotropin response to hypothalamic stimulation with an intravenous bolus of kisspeptin-54 (9.6nmol/kg) and the pituitary response to an intravenous bolus of GnRH (100 mcg). Participants/materials, setting, methods All participants took part in two study visits. Serum luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were measured every 15 minutes for 8 hours after administration of kisspeptin-54 and GnRH. The maximal rise in LH and FSH from baseline was compared between groups using an unpaired t-test. Receiver operator characteristic (ROC) analysis was used to assess the discriminatory potential of the hormone response to kisspeptin and GnRH. Main results and the role of chance The gonadotropin response to kisspeptin was increased in women with FHA compared to all other groups. The mean (SD) of the maximal rise in LH (IU/L) after kisspeptin was 9.7 (11.4) in healthy women, 9.7 (8.3) in women with PCOS, 17.6 (10.8) in women with FHA, and 1.0 (1.1) in women with CHH. The mean (SD) of the maximal rise in FSH (IU/L) after kisspeptin was 4.2 (3.4) in healthy women, 2.8 (2.1) in women with PCOS, 9.2 (5.6) in women with FHA, and 0.7 (0.5) in women with CHH. In lean women (BMI <25 kg/m2), the maximal rise in FSH after kisspeptin differentiated women with PCOS from those with FHA (area under ROC curve 0.91, p = 0.0001). Furthermore, the maximal rise in FSH after kisspeptin differentiated women with FHA from women with CHH (auROC 1.00, p < 0.0001), whereas the equivalent auROC for FSH rise after GnRH was 0.7 (p = 0.086). Limitations, reasons for caution Participants included in this study had clearcut diagnoses of PCOS, FHA, or CHH prior to inclusion, however this could increase the risk of spectrum bias. Whilst this study provides mechanistic insight into hypothalamic dysfunction in these conditions, further prospective validation of discriminatory thresholds in different settings is required. Wider implications of the findings The specific action of kisspeptin at hypothalamic GnRH neurons enables its use to assess hypothalamic function in patients with oligo-amenorrhea due to different anovulatory disorders. Our data suggests that the hormonal response to kisspeptin has promising diagnostic potential to aid in the evaluation of women with oligo-amenorrhea. Trial registration number ISRCTN21681316

GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain.

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

Impact of preovulatory follicle maturity on oocyte metabolism and embryo development.

Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid.

Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics.

In humans, the first 1000 days of life are pivotal for brain and organism development. Shortly after birth, gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus are activated, a phenomenon known as minipuberty. This phenomenon, observed in all mammals studied, influences the postnatal development of the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. This review will put into perspective the results of recent studies showing that the impact of minipuberty extends beyond reproductive function, influencing sensory and cognitive maturation. Studies in mice have revealed the role of nitric oxide (NO) in regulating minipuberty amplitude, with NO deficiency linked to cognitive and olfactory deficits. Additionally, findings indicate that cognitive and sensory defects in adulthood in a mouse model of Down syndrome are associated with an age-dependent decline of GnRH production, whose origin can be traced back to minipuberty, and point to the potential therapeutic role of pulsatile GnRH administration in cognitive disorders. Furthermore, this review delves into the repercussions of COVID-19 on GnRH production, emphasizing potential consequences for neurodevelopment and cognitive function in infected individuals. Notably, GnRH neurons appear susceptible to SARS-CoV-2 infection, raising concerns about potential long-term effects on brain development and function. In conclusion, the intricate interplay between GnRH neurons, GnRH release, and the activity of various extrahypothalamic brain circuits reveals an unexpected role for these neuroendocrine neurons in the development and maintenance of sensory and cognitive functions, supplementing their established function in reproduction. Therapeutic interventions targeting the HPG axis, such as inhaled NO therapy in infancy and pulsatile GnRH administration in adults, emerge as promising approaches for addressing neurodevelopmental cognitive disorders and pathological aging.

Premenstrual syndrome and premenstrual dysphoric disorder-Overview on pathophysiology, diagnostics and treatment

Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as adifferential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From apathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by acomplex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.

GnRH-mediated suppression of S100A4 expression inhibits endometrial epithelial cell proliferation in sheep via GNAI2/MAPK signaling.

Gonadotrophin-releasing hormone (GnRH) administration significantly decreases the pregnancy rate of recipient ewes after embryo transfer, possibly because GnRH affects endometrial epithelial cell function. Therefore, this study investigated the effect of GnRH on endometrial epithelial cells. Transcriptome sequencing was used to determine the regulatory effect of GnRH on the ewe endometrium, and the S100A4 gene, which showed altered transcription, was screened as a candidate regulator of this effect. Endometrial epithelial cells were further isolated, the S100A4 protein was immunoprecipitated, and host proteins that interacted with S100A4 were identified by mass spectrometry. We further verified the effects of S100A4 and GNAI2 on the proliferation of endometrial epithelial cells via overexpression/knockdown experiments and subsequent CCK-8 and EdU assays. The effect of S100A4 deletion in endometrial cells on reproduction was verified in mice with S100A4 knockout. Our results showed that S100A4 gene transcription in endometrial cells was significantly inhibited after GnRH administration. GNAI2 was identified as a downstream interacting protein of S100A4, and S100A4 was confirmed to activate the MAPK signaling pathway to promote cell proliferation by targeting GNAI2. GnRH can suppress the expression of S100A4 in the endometrium, consequently inhibiting the proliferation of endometrial cells through the S100A4/GNAI2/MAPK signaling pathway. These findings suggest a potential explanation for the limited efficacy of GnRH in promoting embryo implantation.

Effect of GnRH on the day of Insemination on Ovulatory Response in Crossbred Cows

The effect of gonadotropin releasing hormone (GnRH) analogue on the ovulatory response of oestrual follicle during cold and hotter months of the year was studied. A total of 120 crossbred cows brought for insemination with oestrus signs during colder months (December 2022 –January 2023; n=52) and hotter months (April – May 2023; n=68) to the Gynaecology Unit of Veterinary Clinical Complex, Veterinary College and Research Institute, Orathanadu were utilized for the study. Oestrus (Day 0) was confirmed by gynaeco-clinical and ultrasound examination and animals were inseminated with (n =33) or without (n = 87) GnRH (Buserelin acetate 10 mcg; im). The biometry of oestrual follicle (OF) and regressing corpus luteum (RCL) were measured ultrasonographically on Day 0 and the OF was observed every 24 hours until ovulation. The diameter of the OF on Day 0 was non-significantly (P > 0.05) larger during hotter months (12.19 ± 0.21 mm) than colder months (11.58 ± 0.32 mm). There were no significant (P > 0.05) differences in the diameter of RCL between the two periods (9.63 ± 0.21 and 9.56 ± 0.22 mm respectively). OFs were observed majorly in the right ovary during the hotter (60.76%) and colder (54.17%) months. Ovulations occurred on the mean days of 1.00 and 1.37 ± 0.18 in GnRH group during hotter (H-Gn) and colder months (C-Gn) respectively. The respective mean days in non-GnRH group were 1.14 ± 0.05 and 1.33 ± 0.08 during hotter (H-O) and colder months (C-O). In H-Gn group all the animals (100%) ovulated on Day 1, when compared to C-Gn animals (62.50%). On perusing the possible effect of RCL on ovulation, significantly increased percentages of ovulations were observed in OFs on the contralateral ovary to the ovary having the RCL in GnRH group and viceversa in non-GnRH group. It could be assumed that GnRH administration on the day of insemination may be beneficial during the hotter months of the year.

EFFECT OF GONADOTROPHIN RELEASING HORMONE ON FOLLICULAR DYNAMICS, LUTEINISING HORMONE, AND PROGESTERONE LEVELS IN BUNAJI COWS

This study evaluated the ovarian and hormonal responses of Bunaji cows to ovsynch protocol initiated at random oestrus cycle stages. Fifteen animals were arranged into three groups and treated as follows: control (n=5), 2mL normal saline; group A (n=5), 50mg Gonadotrophin releasing hormone (GnRH) on day 0 and day 9 followed by 500mg of Prostaglandin F2 alpha (PGF2a) on day 7; and group B (n=5) 100mg of GnRH on day 0 and day 9 followed by 500mg PGF2a on day 7. Ultrasound examination of the ovaries was carried out daily from d 1 to d 9 and, thereafter every 12h until ovulation was detected. Blood sampling was carried out at 30 min intervals for 6 h following the GnRH administration for determination of serum luteinizing hormone (LH) and once daily for 12 days after the injection of the first GnRH to determine plasma progesterone concentration. The ovarian response of the treated groups showed no significant difference between the two dosages of ovsynch protocol but differed significantly between the treated and the control groups. Peak values of serum LH obtained on day 0 and day 9 of GnRH administration differed significantly (P<0.05). Plasma progesterone increased among treated groups following injection of GnRH reaching a peak on day 7 compared to control, but did not differ among treated groups. In conclusion, GnRH at 50 mg and 100 mg was able to elicit adequate LH and progesterone responses that caused the disappearance of dominant follicles and, subsequent ovulation thereby increasing the reproductive efficiency of Bunaji cows.

The Impact of Growth Hormone Co-Treatment Duration on Outcomes in IVF/ICSI Cycles Among Poor Ovarian Responders.

The efficiency of in vitro fertilization is improved by growth hormone (GH) during ovarian stimulation. Additionally, patients with diabetes experience impaired insulin resistance and compromised glucose tolerance, which further exacerbate their condition. Due to these side effects, in this study, the duration of GH treatment was compared in IVF/ICSI cycles among poor ovarian responders. In this study, POSEIDON criteria were used to choose patients. Subcutaneous administration of gonadotropin-releasing hormone (GnRH) antagonist was done beginning on the sixth day of the cycle and continuing through the day of human chorionic gonadotropin (hCG) injection. In one group, GH was administered 4 units/day from the 2nd day of the cycle until hCG injection, and in another group, the first dose was administered on the 6th day of the cycle. Following the administration of hCG, which lasted from 24 to 36 hr, oocytes were retrieved with the support of B-mode sonography. In our analysis, no significant differences were observed between the two groups in terms of the number of retrieved oocytes, metaphase II oocytes, and quality of grade A and B embryos. The results show that the treatment or conditions did not have a significant impact on the outcomes among the studied groups. Our findings indicate that a shorter duration of GH administration can yield similar outcomes compared to a longer duration in IVF/ICSI cycles involving poor ovarian responders. This result holds the potential for a more cost-effective and patient-friendly approach in managing assisted reproductive technology procedures. It may lead to reduced side effects and improved adherence to medication regimens in patients.

Abstract 12107: Cardiovascular Outcomes Associated With Gonadotropin-Releasing Hormone Antagonists vs Gonadotropin-Releasing Hormone Agonists for Prostate Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

Background: Androgen deprivation therapy (ADT), comprising the administration of Gonadotropin-releasing hormone (GnRH) agonists and antagonists, is a widely utilized treatment for prostate cancer patients and has been universally accepted as the first-line treatment for symptomatic metastatic prostatic cancer. While ADT has proven effective, concerns about its impact on cardiovascular health have emerged. Conflicting results regarding the association between ADT and cardiovascular events have been reported in the most recent PRONOUNCE trial hence a meta-analysis to systematically evaluate the evidence is desired. Aim: The primary objective of this meta-analysis was to investigate and compare the effects of GnRH agonists and antagonists on cardiovascular events in patients with prostate cancer. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: 9 studies met the eligibility criteria and were included in the final analysis. A total of 3648 patients were randomized to receive either an agonist (n=1375) or an antagonist (n=2273). The pooled results revealed a significant reduction in the risk of adverse cardiovascular events by 48% with the use of GnRH agonists compared to GnRH antagonists (RR=0.52; 95% CI=0.39-0.71; p<0.01). Furthermore, GnRH agonists also decreased the risk of all-cause mortality by 46% (RR=0.54; 95% CI= 0.33-0.88; p=0.01) and cardiovascular mortality by 78% (RR= 0.22; 95% CI= 0.07-0.76; p=0.02) compared to GnRH antagonists. Conclusion: The findings of this meta-analysis reveal the favorable cardiovascular risk profile associated with GnRH agonists, supporting their role as a preferred treatment option over GnRH antagonists.

292 Tandem Administration of Prostaglandin F2α and Gonadotropin-Releasing Hormone in Beef Heifers and Cows as a Convergent Presynchronization Method in the 7 & 7 Synch Protocol

Abstract An experiment was designed to evaluate modifications to the 7 & 7 synch protocol with the hypothesis that tandem administration of prostaglandin F2α (PG) and gonadotropin-releasing hormone (GnRH) during the presynchronization portion of the protocol would generate a convergent ovarian response among anestrous and estrous cycling females. Nulliparous (n = 153), primiparous (n = 92), and multiparous (n = 413) Angus-cross females across four locations were blocked based on parity and pre-treatment cyclicity status (presence or absence of a corpus luteum) as assessed via transrectal ovarian ultrasonography. Within block, females were randomly assigned to one of three treatments. Females assigned to the 7 & 7 Synch treatment received an intravaginal progesterone-releasing insert (CIDR) and administration of PG on day 0, administration of GnRH on day 7, and administration of PG coincident with CIDR removal on day 14. Females assigned to 7 & 7 Synch + G received the same treatment schedule with the modification that GnRH was administered in tandem with the PG on day 0. Females assigned to 7 & 7 Synch + G + P received GnRH in tandem with PG on both day 0 and day 7 of the treatment schedule. Fixed-time artificial insemination (FTAI) was performed at 54 h after CIDR removal for nulliparous females and at 66 h for primiparous and multiparous females. Transrectal ovarian ultrasonography was performed on day 7 and day 14 to characterize the largest follicle diameter (LFD) as well as the presence/absence and number of corpora lutea (CL). Expression of estrus before FTAI was characterized in three locations using estrus detection patches (Estrotect. Approximately 75 to 90 days after FTAI, pregnancy status was determined via transrectal ultrasonography. Day 7 CL status was affected by treatment (P = 0.002), with a greater proportion of females presenting with CL on Day 7 when treated with the modified treatments (64%) as compared with the 7 & 7 Synch treatment (31%). Day 14 LFD was affected by treatment (P = 0.002), with a larger average LFD among females treated with 7 & 7 Synch + G + P (12.0 mm) as compared with 7 & 7 Synch (11.4 mm) or 7 & 7 + G (10.7 mm). Pregnancy rate to FTAI was affected by pre-treatment cyclicity status (P < 0.0001) and semen type (P = 0.0003) and tended to be affected by treatment (P = 0.09) with 7 & 7 Synch + G + P tending to result in a greater proportion pregnant (58.86%) as compared with 7 & 7 Synch (49.17%) and 7 & 7 Synch + G (48.79%). Tandem administration of GnRH and PG on days 0 and 7 of the 7 & 7 Synch protocol effectively generated a convergent ovarian response among anestrous and estrous cycling beef females and tended to result in increased pregnancy rates to FTAI.

179 Cost and Profit Per Pregnancy Associated with Estrous Synchronization Utilizing Estrus Detection And/Or Fixed-Time Artificial Insemination

Abstract This experiment aimed to compare synchronization cost associated with two protocols: one utilizing estrus detection (6d; PG 6-d CIDR+TAI) and one utilizing strictly fixed-time artificial insemination (FTAI; 7d; 7-d CO-Synch+CIDR). Cows and heifers (n = 657) from 10 herds in three states were grouped by days postpartum and age, and randomly assigned to one of two protocols. Cows and heifers assigned to the 6 d protocol were administered prostaglandin F2α (PGF) on d-9, CIDR insertion and administration of gonadotropin-releasing hormone (GnRH1) on d -6, and CIDR removal and PGF administration on d 0. Cows and heifers that were assigned to the 6-d protocol were subsequently grouped into three treatments based on presence and/or timing of estrus and insemination (PG1: Insemination before CIDR insertion, n = 136; PG2: Insemination after CIDR removal, n = 26; T6: Insemination at TAI, n = 166). Cows and heifers assigned to the 7-d protocol (T7: Insemination at FTAI, n = 329) were administered GnRH1 and CIDR insertion on d -7, followed by CIDR removal and PGF administration on d 0. For all animals, FTAI and GnRH2 administration occurred at 54 h (heifers) or 66 h (cows) after CIDR removal. Pregnancy was determined from d 30 to d 40 after FTAI by transrectal ultrasonography. Total cost and profit per pregnancy was calculated for herds of 30, 100, 300, and 500 females with varying estrus response and pregnancy rates. Expenditures were calculated assuming synchronization costs (PG1 = $46.15, PG2 = $75.05, T6 = $77.91, T7 = $73.72), general labor cost considering herd size and handling days, as well as estrus detection labor cost assuming $10.00 per h, a 95% overall herd pregnancy rate, a 1:40 bull:cow ratio, and average bull purchase price of $3,000.00. Revenue was estimated assuming a maximum 205-d weaning age, 1.09 kg/d gain, $200.00/45.4 kg, and 85% weaning rate. Differences in estrus response and pregnancy rate were determined using the GLIMMIX procedure of SAS (v9.4), including herd as a random variable. Estrus response was greater (P < 0.0001) in females assigned to the 6d (73 ± 4%) compared with the 7d (53 ± 4%) protocol; however, pregnancy success was similar among treatment groups (P = 0.32; PG1 = 45 ± 4%, PG2 = 58 ± 10%, T6 = 46±4%, T7 = 52±3%). At the observed estrus response and pregnancy rate for each treatment group, the 6d protocol resulted in a decreased cost per pregnancy compared with the 7d protocol [Table 1; herds of: 30 = ($3.53), 100 = ($5.16), 300 = ($6.58), 500 = ($7.00) females]. Additionally, using the same variables, the 6d protocol resulted in an increased profit per pregnancy compared with the 7d protocol (herds of: 30 = $3.50, 100 = $6.41, 300 = $17.27, 500 = $12.06 females). These results suggest that labor associated with estrus detection may be offset by the proportion of calves subsequently born earlier within the calving season, allowing for improvements to profitability, especially in larger herds.

Non-Invasive Quantification of Faecal and Urine Reproductive Hormone Metabolites in the Naked Mole-Rat (Heterocephalus glaber).

The naked mole-rat (Heterocephalus glaber) occurs in colonies with a distinct dominance hierarchy, including one dominant, breeding female (the queen), 1-3 breeding males, and non-reproductive subordinates of both sexes that are reproductively suppressed while in the colony. To non-invasively evaluate reproductive capacity in the species, we first had to examine the suitability of enzyme immunoassays (EIAs) for determining progestogen and androgen metabolite concentrations in the naked mole-rat, using urine and faeces. A saline control and gonadotrophin-releasing hormone (GnRH) were administered to twelve (six males and six females) naked mole-rats which were previously identified as dispersers and housed singly. The results revealed that urine is possibly not an ideal matrix for progestogen and androgen metabolite quantification in naked mole-rats as no signal was detected in the matrix post GnRH administration. A 5α-Progesterone EIA and an Epiandrosterone EIA were identified as suitable for quantifying faecal progesterone metabolites (fPMs) and faecal androgen metabolites (fAMs) in males and females, respectively. The results suggest that there are individual variations in baseline fPM and fAM concentrations, and only two out of six females and no males exhibited an increase in fPM concentrations greater than 100% (-20% SD) post GnRH administration. Conversely, only four out of six females and three out of six males had an increase in fAM concentrations greater than 100% (-20% SD) following GnRH administration. These results imply that some naked mole-rat individuals have a reduced reproductive capacity even when they are separated from the queen.

Effect of the GnRH stimulation test on Canine Prostatic-Specific Esterase (CPSE).

The gonadotropin-releasing hormone (GnRH) stimulation test is used to investigate testicular production of testosterone (T) when performing a breeding soundness examination. In male dogs with fertility problems, the prostate should also be investigated as prostatic conditions may frequently lower semen quality. Serum concentrations of canine prostatic-specific esterase (CPSE) increase in dogs with benign prostatic hyperplasia (BPH). When performing a breeding soundness examination in a male dog, GnRH administration is frequently done at the beginning of the process and then both T and CPSE are assayed on the same serum sample collected 1 h following the GnRH injection. The aim of this study was to assess whether or not the administration of GnRH may alter CPSE concentrations in dogs with a healthy prostate. Twenty-eight client-owned intact adult male dogs were included in the study. Following a 7-day sexual rest all male dogs underwent a clinical examination and an ultrasonographic examination of the prostatic gland. Prostatic size and parenchyma of every tested dog were evaluated by ultrasonography to assess prostatic conditions. Two different GnRH stimulation protocols were used, A = gonadorelin 50μg/dog SC (n = 15) and B = buserelin 0.12 μg/kg IV (n = 13). T and CPSE concentrations were measured before and 1 h after GnRH administration by a laser-induced fluorescence analysis. Buserelin and gonadorelin were equally effective in causing a significant increase in serum T concentrations in the post GnRH sample. When considering the 28 dogs together, CPSE concentrations did not change following the stimulation test with either GnRH compound; however, in 4/28 cases, the post GnRH value was markedly increased to values compatible with a diagnosis of BPH. There was no difference in the action of buserelin or gonadorelin in causing an increase in serum T concentrations. CPSE secretion was increased in approximately 15% of dogs treated with either buserelin or gonadorelin. Therefore, whenever performing diagnostic testing in intact male dogs, CPSE should not be assayed on a post-GnRH serum sample.

Three decades of progress in artificial insemination in rabbit farming: a review

The commercial use of artificial insemination (AI) in rabbit farming is relatively recent, especially when compared to other species such as cattle or swine, in which AI has been used for more than 60 years. The large-scale use of AI in rabbit farming dates back to the late 80s. However, despite its short journey, it has not stopped evolving. Although there have been numerous changes, in this review article we aim to highlight two important milestones in optimisation of this technique: the introduction of biostimulation and the addition of Gonadotropin-releasing hormone (GnRH) analogues to the seminal dose to induce ovulation. In the former case, by means of different methods of biostimulation, such as feed and light flushing and/or separation of the litter in the days prior to AI, the use of hormones to synchronise heat with the moment of AI was practically eliminated. Nowadays, the possibility of using pheromones with the same objective is under research, even to increase ovulation rate or improve semen production. Although there are pheromones on the market labelled for use in other species, in the case of rabbit the knowledge of them is limited. Nevertheless, given the verified effects that pheromones produce in other animals, expectations are high. In the latter case, after several attempts by using other methods, the technique commonly used to induce ovulation was the intramuscular administration of GnRH or its synthetic analogues. However, in recent years, it has been proven that administration of GnRH through the vagina is possible, added to the seminal dose, which offers numerous advantages regarding health, animal welfare and the workforce needed. Recently, the European Medicines Agency (EMA) approved this practice, so in the near future it will probably become the most widely used method. Even so, there is still room for improvement, as the dosage of GnRH needed is higher than the one administered intramuscularly. Research on this topic allows us to predict that this problem should be solved in the coming years. Other alternatives such as the β-Nerve Growth Factor need further research to become a feasible option.

Gonadotropin-releasing hormone and growth hormone act as anti-inflammatory factors improving sensory recovery in female rats with thoracic spinal cord injury.

The potential for novel applications of classical hormones, such as gonadotropin-releasing hormone (GnRH) and growth hormone (GH), to counteract neural harm is based on their demonstrated neurotrophic effects in both in vitro and in vivo experimental models and a growing number of clinical trials. This study aimed to investigate the effects of chronic administration of GnRH and/or GH on the expression of several proinflammatory and glial activity markers in damaged neural tissues, as well as on sensory recovery, in animals submitted to thoracic spinal cord injury (SCI). Additionally, the effect of a combined GnRH + GH treatment was examined in comparison with single hormone administration. Spinal cord damage was induced by compression using catheter insufflation at thoracic vertebrae 10 (T10), resulting in significant motor and sensory deficits in the hindlimbs. Following SCI, treatments (GnRH, 60 μg/kg/12 h, IM; GH, 150 μg/kg/24 h, SC; the combination of both; or vehicle) were administered during either 3 or 5 weeks, beginning 24 h after injury onset and ending 24 h before sample collection. Our results indicate that a chronic treatment with GH and/or GnRH significantly reduced the expression of proinflammatory (IL6, IL1B, and iNOS) and glial activity (Iba1, CD86, CD206, vimentin, and GFAP) markers in the spinal cord tissue and improved sensory recovery in the lesioned animals. Furthermore, we found that the caudal section of the spinal cord was particularly responsive to GnRH or GH treatment, as well as to their combination. These findings provide evidence of an anti-inflammatory and glial-modulatory effect of GnRH and GH in an experimental model of SCI and suggest that these hormones can modulate the response of microglia, astrocytes, and infiltrated immune cells in the spinal cord tissue following injury.

New Horizons: Gonadotropin-Releasing Hormone and Cognition.

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal axis, which controls the onset of puberty and fertility. Two recent studies suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition. This review will summarize the development and establishment of the GnRH system, with particular attention to the importance of its first postnatal activation, a phenomenon known as minipuberty, for later reproductive and nonreproductive functions. In addition, we will discuss the beneficial effects of restoring physiological (ie, pulsatile) GnRH levels on olfactory and cognitive alterations in preclinical Down syndrome and Alzheimer disease models, as well as the potential risks associated with long-term continuous (ie, nonphysiological) GnRH administration in certain disorders. Finally, this review addresses the intriguing possibility that pulsatile GnRH therapy may hold therapeutic potential for the management of some neurodevelopmental cognitive disorders and pathological aging in elderly people.

Reproductive Performance of Female Rabbits Inseminated with Extenders Supplemented with GnRH Analogue Entrapped in Chitosan-Based Nanoparticles.

Rabbit is a reflexively ovulating species. Accordingly, in the practice of artificial insemination (AI) ovulation must be induced via exogenous GnRH (Gonadotropin-Releasing Hormone) administration, which may be performed intramuscularly, subcutaneously, or intravaginally. Unfortunately, the bioavailability of the GnRH analogue when added to the extender is lower due to the proteolytic activity in the seminal plasma and the poor permeability of the vaginal mucosa. The aim of the study was to refine the practice of AI practice in rabbits by replacing parenteral GnRH analogue administration (subcutaneous, intravenous, or intramuscular injection) with intravaginal application, while reducing its concentration in the diluent. Extenders containing the buserelin acetate in chitosan-dextran sulphate and chitosan-alginate nanoparticles were designed and 356 females were inseminated. Reproductive performance of females inseminated with the two experimental extenders, receiving 4 μg of buserelin acetate intravaginally per doe, was compared with that in the control group, the does of which were inseminated with the extender without the GnRH analogue and induced to ovulate with 1 μg of buserelin acetate administered intramuscularly. The entrapment efficiency of the chitosan-dextran sulphate complex was higher than that of chitosan-alginate. However, females inseminated with both systems showed similar reproductive performance. We conclude that both nanoencapsulation systems are an efficient way of intravaginal ovulation induction, allowing a reduction in the level of the GnRH analogue normally used in seminal doses from 15-25 μg to 4 μg.

Economical implications and the impact of gonadotropin-releasing hormone administration at the time of artificial insemination in cows raised in the extensive system in North Romania.

Artificial insemination (AI) is the first and the most used biotechnologies in reproduction all over the world. Many studies reported the beneficial role of gonadotropin-releasing hormone (GnRH) administrated some hours before the AI or at the artificial insemination time. This study aimed to assess the effect of GnRH analogs given at the time of insemination on the first, second, and third AIs and to assess the economical implications of GnRH administration. We hypothesized that administration of GnRH at the time of insemination would increase ovulation and pregnancy rate. The study was conducted on small farms in northwestern Romania and included animals of the Romanian Brown and Romanian Spotted breeds. Animals in estrous at the first, second, and third inseminations were randomly divided into groups that received GnRH at insemination and groups that did not. A comparison between the groups was performed and the cost of GnRH administration to obtain one gestation was calculated. The GnRh administration increased the pregnancy rate at the first and the second inseminations by 12 and 18%, respectively. For one pregnancy, the cost of GnRH administration was approximately 49 euros for the first insemination group and around 33 euros for the second insemination group. No improvement of the pregnancy rate was observed after the GnRH administration for the cows at the third insemination, so, for this group, no economic statistics were performed.

Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis.

Endometriosis, defined as the development of endometrial tissue outside of the uterine cavity, is a common gynecological disorder. The prevalence of pelvic endometriosis approaches 6%-10% in the general female population, and in women with pain, infertility, or both, the frequency is 35%-50%. The gold standard recommended process for diagnosing endometriosis is laparoscopy, an invasive surgical procedure, with or without histologic verification. The currently available nonsurgical treatments include oral contraceptives (estrogen-progestogen preparations), progestogen preparations (containing progesterone derivatives), androgenic hormones (danazol), and gonadotropin-releasing hormone (GnRH) agonists and antagonists. Two GnRH types have been discovered in mammals, GnRH I and GnRH II. In particular, GnRH I is released by the hypothalamus; however, it can be present in various tissues and organs of the body, including neural tissue, where it exerts neuroendocrine, autocrine, and paracrine actions in the peripheral and central nervous system (CNS). Interestingly, another GnRH isoform, GnRH III, has been identified, which has 60% similarity with GnRH I from which it varies by four amino acids. This peptide has been shown to have a significant role in reproduction, specifically in gametogenesis and steroidogenesis. Further research is needed to identify innovative treatment options for endometriosis, such as the therapeutic exogenous administration of GnRH II or antagonists of the GnRH I receptor. In this review, we examined the role of GnRH in endometriosis, outlining the specific actions of GnRH and GnRH receptors (GnRHRs). The innovative use of GnRH analogs and antagonists in the treatment of endometriosis is also discussed.