Gonadorelin Research & Studies

This study evaluated the influence of GnRH analogs (gonadorelin vs. buserelin) and doses (single vs. double) on LH release and ovulatory response in Bos indicus (Nelore) females on Day 7 of the estrous cycle. Cycling heifers and non-lactating cows were pre-synchronized: Day -10: progesterone (P4) implant insertion plus 2 mg of estradiol benzoate; Day -2: implant removal and 0.53 mg of cloprostenol sodium (PGF); Day 0: 25 μg of lecirelin (GnRH). Over four replicates, heifers (n = 57) and cows (n = 53) that ovulated to the GnRH treatment on Day 0, having a visible corpus luteum (CL) and a dominant follicle (DF) ≥ 8.5 mm, were allocated to receive the following GnRH treatments on Day 7: G-Single (100 μg of gonadorelin); G-Double (200 μg of gonadorelin); B-Single (10 μg of buserelin); and B-Double (20 μg of buserelin). At GnRH treatment, a P4 implant was inserted in heifers (0.5 g) and cows (1 g). Ultrasound examinations were done on Days -10, -2, 0, 2, 7, 9, 12, and 14 to evaluate DF diameter, ovulation and presence of CL. Blood samples were collected on Day 7 at 0, 2, and 4 h from GnRH treatment, to evaluate circulating P4 and LH concentrations. On Day 12, the P4 implant was removed, females received two PGF treatments (24 h apart), and 2 d later, 25 μg of GnRH was given to start the next replicate. In both heifers and cows, P4 concentrations were elevated on Day 7, and similar among groups (3.9 and 4.2 ng/mL, respectively). In heifers, buserelin induced greater LH peak (9.5 vs. 2.6 ng/mL; P < 0.01) and greater ovulation (88.9 [24/27] vs. 16.7% [5/30]; P < 0.01) than gonadorelin treatments, regardless of the dose. Similarly, in cows, buserelin induced greater LH peak than gonadorelin (9.9 vs. 4.9 ng/mL; P < 0.01). However, ovulation was only increased in cows from the B-Double group (90.9% [10/11]), whereas in the other groups the ovulatory response was similar (35.7% [15/42]). Regardless of treatment, heifers had similar P4 concentrations (P = 0.22), but smaller DF (P < 0.01) than cows on Day 7. Only in G-Double group the LH peak was lower (P = 0.05) in heifers than in cows, with no difference within other groups. In heifers, but not in cows, the single dose of buserelin resulted in high ovulatory response, equivalent to that produced by the double dose. In conclusion, in Bos indicus heifers and cows on Day 7 of the cycle, with elevated P4 concentrations, buserelin induced greater LH release and ovulatory response than gonadorelin treatments. Double doses increased the LH release, however, only resulted in greater ovulation in females treated with buserelin. Finally, although circulating P4 concentrations did not differ between parities, heifers were more likely to ovulate in response to a GnRH-induced LH peak than cows.

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.

Difference in breed, nutrition status and climate in which animals are managed result in differences in response to reproductive hormones. Fertility rate to artificial insemination is very low in Ethiopian Boran and Boran*Holstein crosses. This partly maybe due to adopting estrus and/or ovulation synchronization developed for temperate taurine cattle. Experimental study was conducted to evaluate ovarian response to combinations of Gonadotrophin-Realizing Hormone agonist (gonadorelin) and ProstaglandinF2α (PGF2α) with or without progesterone (Controlled Internal Drug Release/CIDR), and conception rate to timed AI. Postpartum native Ethiopian Boran (n = 60) and Boran*Holstein cross (n = 66) cows were randomly assigned to four treatment groups as Ovsynch (gonadorelin on day of start, PGF2α seven days later, 2nd gonadorelin at 48 h of PGF2α and insemination at 19 h of the 2nd gonadorelin); CIDR + Ovsynch (same as Ovsynch but CIDR device was inserted into vagina for 7 days); Cosynch (same as Ovsynch but insemination was made at the 2nd gonadorelin) and CIDR + Cosynch (same as Cosynch but CIDR was inserted for 7 days).

In the last twenty years, we have witnessed an important evolution of bioanalytical approaches moving from conventional lab bench instrumentation to simpler, easy-to-use techniques to deliver analytical responses on-site, with reduced analysis times and costs. In this frame, affinity reagents production has also jointly advanced from natural receptors to biomimetic, abiotic receptors, animal-free produced. Among biomimetic ones, aptamers, and molecular imprinted polymers (MIPs) play a leading role. Herein, our motivation is to provide insights into the evolution of conventional and innovative analytical approaches based on chromatography, immunochemistry, and affinity sensing referred to as peptide hormones. Indeed, the analysis of peptide hormones represents a current challenge for biomedical, pharmaceutical, and anti-doping analysis. Specifically, as a paradigmatic example, we report the case of gonadorelin, a neuropeptide that in recent years has drawn a lot of attention as a therapeutic drug misused in doping practices during sports competitions.

The standard treatment for boys with non-syndromic cryptorchidism is an early orchidopexy. It is unclear if surgical intervention alone is enough for future fertility. Recent studies show benefit of neoadjuvant or adjuvant hormonal treatment with gonadorelin (GnRH) for spermatogonia maturation based on testicular biopsy. The aim of this prospective study was to assess the safety of this treatment in infants with undescended testis at the recommended timing of early gonadorelin administration and timing of orchidopexy.

Sustained release lipid microparticles for a potential veterinary application were produced by the means of spray congealing using saturated triglycerides with respective surfactants. The spray congealing process was optimized using unloaded and loaded microparticles, revealing the highest impact of the spray flow on material loss. Yield could be optimized by increasing the spray flow as well as a reduction of the melt temperature from 90 to 75 °C. For the delivery system developed in this study, a release of around 15 days was targeted. The release profile was in first hand determined with the use of model substances (aspartame and tryptophan), before incorporating the decapeptide Gonadorelin [6-D-Phe]. Release could be controlled between 2 and 28 d, which was dependent on stability of microparticles upon incubation, type and concentration of emulsifier, as well as the used triglyceride. Differential scanning calorimetry and X-ray powder diffraction confirmed the crystallization behavior of C14 and C16-triglycerides in combination with various emulsifiers in different modification without impact on release.

Analogs of gonadoliberin (GnRH) are widely used in cattle to synchronize estrus and to induce ovulation, as well as for the treatment of ovarian cysts. The aim of this study was to compare the plasma profiles of LH and progesterone and the follicular dynamics in response to the administration of gonadorelin, lecirelin, or buserelin at the dose recommended to induce ovulation. In addition, the biological response to a half dose of lecirelin was assessed. Twelve healthy Holstein female cows were divided into four sequence groups, according to a Latin square design and received the four treatments during the four periods of the study. Before each period, the estrous cycle was synchronized, and on Day 6 or 7 of the ensuing cycle, the time at which it was most likely to have a dominant follicle, 100 μg of gonadorelin, 25 μg of lecirelin, 50 μg of lecirelin, or 10 μg of buserelin was administered to the cows. Blood samples were regularly collected for up to 4 days after the GnRH administrations. The plasma LH response was evaluated for up to 6 hours after administration, and the plasma progesterone response and ovarian follicular dynamics were evaluated for up to 4 days. There was a significantly lower LH release after gonadorelin treatment compared to lecirelin at the doses of 25 or 50 μg and the buserelin treatment. The mean maximal LH concentration after gonadorelin treatment was 2.5 lower than after lecirelin or buserelin treatment and was reached 1 hour earlier. Four days after the GnRH administration (i.e., at Days 10-11 of the estrous cycle), the overall mean increase in plasma progesterone concentration was 70% and did not differ between the treatment groups. The percentage of disappearance of the dominant follicle (84.8% of ovulation and 4.3% of luteinization) after GnRH treatment was high (73%, 82%, 100%, and 100%, for gonadorelin, lecirelin at the doses of 25 and 50 μg, and buserelin, respectively) and did not differ between the GnRH treatments. The follicle disappearance was followed by the emergence of a synchronous follicle wave within 2 days in almost all the heifers. Altogether, our data show that the three GnRH analogs, at the doses indicated for the induction of ovulation or at a half dose for lecirelin, are almost equally effective to induce the disappearance of the dominant follicle at Day 6 to 7 of the estrous cycle.

Gonadotropin-releasing hormone analogues are generally regarded as safe drugs. Gonadorelin acetate has been widely used for the diagnosis of central precocious puberty, and life-threatening reactions to gonadorelin acetate are extremely rare. Herein, we described - to the best of our knowledge - the first pediatric case in which severe anaphylaxis was encountered after intravenous gonadorelin acetate administration. An 8-year-old girl who was diagnosed with central precocious puberty was receiving triptorelin acetate treatment uneventfully for 6 months. In order to evaluate the efficacy of the treatment, an LH-RH stimulation test with gonadorelin acetate was planned. Within 3 min after intravenous administration of gonadorelin acetate, she lost consciousness and tonic seizures began in her hands and feet. She was immediately treated with epinephrine, diphenhydramine, and fluids. Her vital signs recovered within 30 min. Based on the results, anaphylaxis should be anticipated and the administration of these drugs should be performed in a setting that is equipped to deal with systemic reactions.

Studies suggest that estrogen plays a contributing role in colorectal cancer. This project examined the preventive effects of raloxifene, a selective estrogen receptor modulator (SERM), and gonadorelin, an antiestrogenic drug, in female Apc(Min/+) mouse intestinal tumorigenesis. Six-week-old Apc(Min/+)mice were fed diet containing 1 ppm raloxifene or control diet. Gonadorelin (150 ng/mouse) was injected subcutaneously into one treatment group. Intestinal tumors were evaluated for tumor multiplicity and size. Mice treated with raloxifene and gonadorelin showed colon tumor inhibition of 80% and 75%, respectively. Both drugs significantly inhibited small intestinal tumor multiplicity and size (75%-65%, P < 0.0001). Raloxifene and gonadorelin showed significant tumor inhibition with 98% and 94% inhibition of polyps >2 mm in size. In mice fed with raloxifene or injected with gonadorelin, tumors showed significantly reduced proliferating cell nuclear antigen expression (58%-65%, P < 0.0001). Raloxifene treatment decreased β-catenin, cyclin D1, laminin 1β, Ccl6, and stem-like cells (Lgr 5, EpCAM, CD44/CD24), as well as suppressed inflammatory genes (COX-2, mPGES-1, 5-LOX,). Gonadorelin showed significant decrease in COX-2, mPGES-1, iNOS, and stem-like cells or increased NK cells and chemokines required for NK cells. Both drugs were effective in suppressing tumor growth albeit with different mechanisms. These observations show that either suppression of estrogen levels or modulation of estrogen receptor dramatically suppresses small intestinal and colonic tumor formation in female Apc(Min/+) mice. These results support the concept of chemoprevention by these agents in reducing endogenous levels of estrogen or modulating ER signaling.

To assess the diagnostic value of the simplified gonadorelin stimulation test for precocious puberty.

The degradation kinetics of gonadorelin were investigated systematically with reversed-phase high-performance liquid chromatography. The stability-indicating properties of this system were checked with photodiode array detection and by comparison with capillary zone electrophoretic analysis. Influences of gonadorelin concentration, pH, temperature, buffer ions, and ionic strength on the degradation kinetics were studied. The pH-log Kobs profile can be divided into three parts, a proton, a solvent, and a hydroxyl-catalyzed section, with different degradation products. These degradation products were characterized by mass using LC-MS. Gonadorelin is most stable at pH 5-5.5 with a half-life of 70 days at 70 degrees C. The overall degradation rate constant as a function of the temperature under acidic and alkaline conditions obeys the Arrhenius equation. The gonadorelin concentration and the concentrations of acetate, phosphate, borate, and carbonate buffer have no influence on the decomposition rate of the analyte. Increasing ionic strength led to higher Kobs at pH 2 and lower Kobs at pH 9, but influences were relatively small.

Gonadotropin-releasing hormone (GnRH), a decapeptide synthesized and released by the hypothalamus, regulates production and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the adenohypophysis. Parenterally administered GnRH was initially used diagnostically as a test of adenohypophyseal reserve of LH and FSH. Subsequently, native GnRH was used therapeutically to treat hypothalamic hypogonadal and infertility states in both men and women. Because of the low potency and short half-life of native GnRH, long-acting, potent analogs have been developed that suppress secretion of native pituitary gonadotropins, resulting in medical gonadectomy. When administered parenterally and, more recently, intranasally, these compounds are useful in the management of prostate and breast carcinoma, endometriosis and uterine leiomyomata, precocious puberty and nontumorous ovarian hyperandrogenic syndromes.