157 Effect of a slow-release gonadotrophin-releasing hormone analogue on ovarian activity and oestrous behaviour in mares

2020 ◽  
Vol 32 (2) ◽  
pp. 205
Author(s):  
M. Kaps ◽  
C. Gautier ◽  
C. Cardoso Okada ◽  
J. Kuhl ◽  
J. Aurich ◽  
...  

Oestrus behaviour in mares can contribute to problems in their handleability and reduced performance in equestrian sports. Therefore, methods of transient suppression of oestrous cyclicity in mares are of interest. The aim of our study was to determine whether treatment of mares with slow-release implants containing the gonadotrophin-releasing hormone (GnRH) analogue deslorelin downregulates pituitary GnRH receptors and reduces ovarian function and oestrous behaviour. Shetland mares (age=11.0±1.4 years; bodyweight=185.5±7kg) were oestrous synchronised with two injections of the prostaglandin F2α analogue luprostiol (3.725mg) at an interval of 12 days. One day after the second injection (Day 0), mares were randomly assigned to three groups: slow-release implant with 9.4mg of deslorelin (Suprelorin, Virbac; group D1; n=6), implant with 4.7mg of deslorelin (group D2; n=5), and intramuscular injection of 1.25mg of short-acting deslorelin (control, group C; n=5). Collection of blood samples for analysis of progesterone, LH, and anti-Müllerian hormone (AMH) using established and validated enzyme immunoassays (Scarlet et al. 2018 Theriogenology 117, 72-77), testing for oestrus-like behaviour with a Shetland stallion, and ultrasonography of the genital tract were performed at 2-day intervals until Day 10 after treatment and at 5-day intervals from there. On Days 10 and 45 after treatment, LH stimulation tests with the GnRH agonist buserelin (4µg IV) were performed. Data were normally distributed; differences among groups were analysed using analysis of variance and subsequent Tukey test. Values are means±s.e.m. In all mares without a corpus luteum on Day 0 (progesterone <1ngmL−1; one mare in group D1 and two in group C), ovulation was detected within 9 days after deslorelin treatment. These ovulations were classified as deslorelin induced, whereas ovulations after Day 10 were classified as spontaneous ovulations. The mean interval from deslorelin until the first spontaneous ovulation was 62.0±8.6, 44.2±14.1, and 22.2±3.1 days in groups D1, D2, and C (P<0.05), respectively. Subsequent oestrous cycles were regular. Oestrus-like behaviour until day 50 was reduced in groups D1 (2.0±0.9 days) and D2 (2.4±1.3 days) compared with group C (6.4±1.2 days; P<0.05). Concentration of plasma LH and AMH decreased in group D1 (P<0.05) but not in groups D2 and C. The GnRH stimulation test on Day 10 resulted in an increase (P<0.001) in plasma LH concentration in group C but not in groups D1 and D2 (treatment×time P<0.05). On Day 45, LH concentration increased in all mares in response to buserelin (NS among groups). Within 100 days of treatment, LH concentrations but not AMH concentrations in mares of group D1 returned to baseline. In conclusion, deslorelin slow-release implants transiently suppress ovarian function and oestrus behaviour in mares. Spontaneous ovulation is delayed in a dose-dependent manner. A decrease in AMH concentration suggests inhibitory effects of deslorelin on small antral follicles. Long-term effects on follicular dynamics and fertility in larger horses also need to be assessed.

1994 ◽  
Vol 80 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Emilio Bajetta ◽  
Luigi Celio ◽  
Nicoletta Zilembo ◽  
Aldo Bono ◽  
Domenico Galluzzo ◽  
...  

Aims and background Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer. Methods A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment. Results Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients. Conclusions Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.


2021 ◽  
Vol 33 (2) ◽  
pp. 163
Author(s):  
F. Encinas ◽  
M. Rojas ◽  
L. Dawson ◽  
E. Loetz

Gonadotrophin-releasing hormone (GnRH) or equine and human chorionic gonadotrophins (eCG and hCG) were evaluated for oestrus/ovulation synchronization (E/OS), as well as the influence of GnRH 5 days post-breeding (dpb) on embryo viability (EV), and progesterone (P4) levels on Day 16 and 30 after laparoscopic AI (LAI) or natural service (NS). Fifty-four lactating/non-lactating Alpine breed goats (average of 3.82±1.2s.d. years of age) of mixed parity were E/OS during the early transitional breeding phase using 12±1 day of 300mg of P4 and 2mL of prostaglandin F2α analogue given at P4 removal. The experiment included a sub-group from a larger study in which a completely randomised design was used. The germane data were arranged as a 2×2×2 factorial. This study focused on goats receiving 120IU of eCG and 60IU of hCG (n=40), or GnRH analogue (n=14) 24h after P4 removal. At 5 dpb, 25 goats received 1mL (IM) of GnRH and the control (n=29) received 1mL of physiologic saline. Goats were time-bred 48h after P4 withdrawal by LAI (n=33) or NS (n=21). Pregnancy was diagnosed at 18 to 24, 30, and 40 dpb by non-return to oestrus, pregnancy-specific protein B, and ultrasound, respectively. EV was evaluated as the difference between pregnancy diagnosis results. Blood serum P4 was evaluated at 5, 16, and 30 dpb. A logistic regression model was used for statistical analysis. Pregnancy rate (PR) for LAI or NS, at 18–24, 30, and 40 days was 73 vs. 76%, 67 vs. 62%, and 64 vs. 67%, respectively (P>0.72). In contrast, when GnRH was used for E/OS, the 5 dpb GnRH influenced EV at 30 days (95 vs. 81%; P=0.06) but not at 40 days (89 vs. 86%; P>0.35), compared with placebo. Similarly, with the exception of PR at 40 days (43 vs. 72%; P=0.05), for the GnRH and eCG/hCG E/OS groups, respectively, PR was not affected (P>0.12) by either E/OS or GnRH 5 dpb or their interaction (P>0.35) at any pregnancy diagnosis (i.e. 18–24, 30, or 40 dpb). Likewise, levels of P4 at 5, 16, and 30 dpb did not affect PR at 18–24, 30, and 40 dpb (P>0.92, 0.71, and 0.11). As shown in Table 1, the level of P4 was not influenced for goats receiving GnRH or placebo at 5, 16, or 30 dpb. The baseline mean P4 blood serum level for goats receiving GnRH 5 dpb differed at 16 but not at 30 dpb (P<0.001). Table 1 Blood serum progesterone (P4, ng mL−1) in response to gonadotrophin-releasing hormone (GnRH) or placebo given 5 days post-breeding Sampling day GnRH Placebo P >1 Mean ±SE Mean ±SE 5 (baseline) 6.2a 0.83 5.7a 0.72 0.66 16 11.7b 1.11 11.0b 1.05 0.65 30 6.2a 0.89 7.6c 0.84 0.26 a–cMean values with different superscripts within a column signify statistical difference for GnRH (P<0.001) and placebo (P<0.02). 1Probability for mean differences in the same row.


1995 ◽  
Vol 145 (3) ◽  
pp. 501-511 ◽  
Author(s):  
K Goto ◽  
F Kotsuji ◽  
T Tominaga

Abstract The effects of gonadotrophin-releasing hormone analogue (GnRHa; buserelin) on the pituitary function and morphology of food-restricted rats were compared with those of authentic GnRH. After adult female rats had been restricted to 10 g food/day for 60 days, various doses of GnRHa (10 ng, 100 ng and 1 μg) or GnRH (10 μg) were administered either daily for 7 days or twice a week for 4 weeks from day 61 of the period of underfeeding. Underfeeding brought about a decrease in the pituitary gonadotrophin content, serum levels of gonadotrophins and oestradiol, and the number and size of both LH- and FSH-positive pituitary cells. Daily and/or twice-weekly administration of authentic GnRH to underfed rats produced an increase in pituitary and serum gonadotrophin levels and the number and size of both LH- and FSH-positive pituitary cells. The administration of GnRHa daily for 7 days increased serum gonadotrophin levels, while it produced a reduction in the pituitary gonadotrophin content and number and size of both LH- and FSH-positive pituitary cells in a dose-dependent manner. Twice-weekly administration of GnRHa also produced an elevation of serum gonadotrophin levels and reduction of pituitary gonadotrophin content, although it did not affect the numbers and areas of LH- and FSH-positive pituitary cells. A GnRH loading test performed after the GnRHa treatment showed that the GnRHa treatment performed in this study did not produce down-regulation of the GnRH receptor. Thus, it can be concluded that the gonadotrophin-synthesizing activity of GnRHa is weaker than that of authentic GnRH, or that GnRHa may preferentially exert gonadotrophin-releasing activity rather than gonadotrophin-synthesizing activity in the anterior pituitary of underfed rats. Journal of Endocrinology (1995) 145, 501–511


2013 ◽  
Vol 25 (1) ◽  
pp. 273
Author(s):  
K. Imai ◽  
S. Sugimura ◽  
M. Ohtake ◽  
Y. Aikawa ◽  
Y. Inaba ◽  
...  

We previously reported that follicular wave synchronization and follicular growth treatment (FGT) before ovum pick-up (OPU) were effective in improving oocyte competence, which was associated with an increase in related embryos obtained by somatic cell nuclear transfer (Sugimura et al. 2012 Cell. Reprogram. 14, 29–37). However, oxygen consumption in oocytes remained unknown. The present study was designed to examine the differences in oxygen consumption between bovine oocytes obtained by OPU with or without FGT after in vitro maturation. Holstein dry cows (n = 8) were reared under the same feeding and environmental conditions. Two OPU sessions were conducted in each cow to collect immature oocytes, as described by Sugimura et al. (2012). The first OPU session (OPU group) was performed in cows on arbitrary days of the oestrous cycle, using a 7.5-MHz linear transducer with the needle connected to an ultrasound scanner. Follicles larger than 8 mm in diameter were then aspirated and a controlled internal drug release device (CIDR) was inserted on Day 5 (the day of the first OPU session = Day 0). Then 30 Armour units (AU) of FSH (Antrin, Kyoritsu Seiyaku, Tokyo, Japan) was administrated to cows twice a day from Day 7 to 10 in decreasing doses (6, 6, 4, 4, 3, 3, 2, 2 AU day–1). Cloprostenol (prostaglandin F2α; 0.75 mg) was administered in the morning of Day 9. The second OPU session (FGT-OPU group) was performed 48 h after prostaglandin F2α administration (Day 11), and only follicles larger than 5 mm in diameter were aspirated. The CIDR was removed from the cows just before OPU. Collected cumulus–oocyte complexes in the OPU and FGT-OPU groups were matured in vitro as described by Imai et al. [2006 J. Reprod. Dev. 52(Suppl.), S19–S29]. To collect in vivo-matured oocytes (control group), the CIDR was inserted into the cows on arbitrary days of the oestrous cycle (= Day 0), and oestradiol benzoate (0.8 mg) was administered on Day 1. The cows received the FGT treatment (as described above) from Day 6 to 10; however, the CIDR was removed in the evening of Day 8. Buserelin (gonadotropin-releasing hormone; 200 µg) was then administrated in the morning of Day 10, and OPU was performed at 24 h after gonadotropin-releasing hormone administration (Day 11). Oxygen consumption of matured oocytes was measured noninvasively with a scanning electron microscopy system (HV-405SP; Hokuto Denko Co., Tokyo, Japan). Data were analysed by ANOVA followed by a Tukey-Kramer test. There was no difference in the mean oxygen consumption between the FGT-OPU group (0.34 ± 0.02 × 10–14 mol–1, mean ± SEM) and control group (0.40 ± 0.01 × 10–14 mol–1). However, oxygen consumption in the FGT-OPU and control groups was significantly lower (P < 0.01) than that in the OPU group (0.50 ± 0.02 × 10–14 mol–1). These results revealed significantly lower oxygen consumption in OPU-derived in vitro-matured bovine oocytes after FGT treatment compared with those obtained without FGT treatment. Oxygen consumption of oocytes obtained from FGT-OPU was similar to that of in vivo-matured oocytes, which may reflect their cytoplasmic maturation status with high developmental competence.


1995 ◽  
Vol 132 (1) ◽  
pp. 91-96 ◽  
Author(s):  
John AM Mattheij ◽  
Hans JM Swarts

Mattheij JAM, Swarts HJM. Induction of luteinized unruptured follicles in the rat after injection of luteinizing hormone early in pro-oestrus. Eur J Endocrinol 1995;132:91–6. ISSN 0804–4643 The cause of formation of luteinized unruptured follicles (LUF) is unknown. Formation of LUF was studied after injection of a varying small dose of luteinizing hormone (LH) with or without subsequent injection of gonadotrophin-releasing hormone (GnRH); in addition, the effect of suppression of prolactin on LUF formation was studied. Luteinization without ovulation occurred in virtually all graafian follicles, if 0.5–1.0 μg of LH was injected some hours before the presumed endogenous LH surge (suppressed by Nembutal); with increasing doses of LH progressively increasing numbers of ovulations were observed. If in early pro-oestrus 1 μg of GnRH was given 4 h after 1 μg of LH, formation of LUF was partly prevented; if the interval between LH and GnRH was 8 h or more, the great majority of graafian follicles developed into LUF. If early in pro-oestrus 1 μg of LH was given and 8 h later 0.1 μg of a potent GnRH analogue, about 50% of the follicles became LUF; in similarly treated rats, suppression of prolactin by ergocryptine reduced but did not prevent LUF formation. The data support the idea that deficient LH secretion in the period before ovulation may be involved in the formation of LUF. John AM Mattheij, Department of Human and Animal Physiology, Haarweg 10, 6709 PJ Wageningen, The Netherlands


1986 ◽  
Vol 110 (1) ◽  
pp. 145-150 ◽  
Author(s):  
G. R. Marshall ◽  
F. Bint Akhtar ◽  
G. F. Weinbauer ◽  
E. Nieschlag

ABSTRACT If the suppressive effects of gonadotrophin-releasing hormone (GnRH) antagonists on gonadotrophin secretion are mediated through GnRH-receptor occupancy alone, it should be possible to restore serum gonadotrophin levels by displacing the antagonist with exogenous GnRH. To test this hypothesis, eight adult crab-eating macaques (Macaca fascicularis), weight 4·7–7·6 kg, were subjected to the following treatment regimens. A GnRH-stimulation test was performed before and 4, 12 and 24 h after a single s.c. injection of the GnRH antagonist (N-Ac-d-p-Cl-Phe1,2,d-Trp3,d-Arg6,d-Ala10)-GnRH (ORG 30276). The stimulation tests were performed with 0·5, 5·0 or 50 μg GnRH given as a single i.v. bolus. Blood was taken before and 15, 30 and 60 min after each bolus for analysis of bioactive LH and testosterone. The GnRH-challenging doses were given as follows: 0·5 μg GnRH was injected at 0 and 4 h, followed by 5·0 μg after 12 h and 50 μg after 24 h. One week later, 5·0 μg GnRH were given at 0 and 4 h, followed by 50 μg after 12 h and 0·5 μg after 24 h. Finally, after another week, the GnRH challenges began with 50 μg at 0 and 4 h, followed by 0·5 μg at 12 h and 5·0 μg at 24 h. This design permitted comparison of the LH and testosterone responses with respect to the dose of GnRH and the time after administration of GnRH antagonist. The areas under the response curves were measured and statistical evaluation was carried out by means of non-parametric two-way analysis of variance followed by the multiple comparisons of Wilcoxon and Wilcox. Four hours after the antagonist was injected, the LH and testosterone responses to all three doses of GnRH were suppressed. At the lowest dose of GnRH (0·5 μg) the responses remained reduced even after 24 h, whereas the higher doses of GnRH elicited an LH and testosterone response at 12 and 24 h which was not significantly different from that at 0 h. These data demonstrate that the suppression of LH secretion by a GnRH antagonist in vivo can be overcome by exogenously administered GnRH in a dose- and time-dependent manner, thus strongly supporting the contention that GnRH antagonists prevent gonadotrophin secretion by GnRH-receptor occupancy. J. Endocr. (1986) 110, 145–150


1990 ◽  
Vol 127 (1) ◽  
pp. 149-159 ◽  
Author(s):  
S. Muttukrishna ◽  
P. G. Knight

ABSTRACT Primary cultures of ovine pituitary cells (from adult ewes) were used to investigate the actions of steroid-free bovine follicular fluid (bFF) and highly-purified Mr 32 000 bovine inhibin on basal and gonadotrophin-releasing hormone (GnRH)-induced release of FSH and LH. Residual cellular contents of each hormone were also determined allowing total gonadotrophin content/well to be calculated. As in rats, both crude and highly purified inhibin preparations promoted a dose (P < 0·001)- and time (P < 0·001)-dependent suppression of basal and GnRH-induced release of FSH as well as an inhibition of FSH synthesis, reflected by a fall in total FSH content/well. However, while neither inhibin preparation affected basal release of LH or total LH content/well, GnRH-induced LH release was significantly (P< 0·001) increased by the presence of either bFF (+ 75%) or highly-purified inhibin (+ 64%) in a dose- and time-dependent manner. This unexpected action of bFF on GnRH-induced LH release was abolished in the presence of 5 μl specific anti-inhibin serum, confirming that the response was indeed mediated by inhibin. Furthermore, neither oestradiol-17β (1 pmol/l–10 nmol/l) nor monomeric α-subunit of bovine inhibin (2·5–40 ng/ml) significantly affected basal or GnRH-induced release of LH. These in-vitro findings for the ewe lend support to a number of recent in-vivo observations and indicate that, in addition to its well-documented suppressive effect on the synthesis and secretion of FSH, inhibin may actually facilitate LH release in this species, in marked contrast to its action in the rat. Journal of Endocrinology (1990) 127, 149–159


1986 ◽  
Vol 111 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Alessandro Mongioi ◽  
Grazia Maugeri ◽  
Maria Macchi ◽  
Aldo Calogero ◽  
Enzo Vicari ◽  
...  

Abstract. A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 μg was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P < 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4. 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P < 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P <0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.


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