Pituitary and testicular endocrine responses to exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone in male dogs treated with GnRH agonist implants (original) (raw)
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Reproduction in Domestic Animals, 2009
We tested the effect of dose of GnRH superagonist on pituitary and testicular function in a study with four groups of four male dogs. The Controls received blank implants and the other three groups received implants containing 3, 6 or 12 mg deslorelin (D-Trp 6 -Pro 9 -des-Gly 10 -GnRH ethylamide). In all deslorelin-treated groups, there was initially an acute increase in plasma concentrations of LH and testosterone, followed by declines such that both hormones became undetectable after approximately 12 days. There was a doseresponse in some of these early aspects of the hormone profiles. With respect to long-term effects of treatment, the 12-mg dose had significantly greater effects than the smaller doses for the duration of minimum testicular volume [366 ± 77, mean ± -SEM (3 mg), 472 ± 74 (6 mg), and 634 ± 59 (12 mg) days], absence of ejaculate [416 ± 88 (3 mg), 476 ± 83 (6 mg), and 644 ± 67 (12 mg) days], undetectable plasma concentrations of LH and testosterone [367 ± 64 (3 mg), 419 ± 72 (6 mg), and 607 ± 69 (12 mg) days], the delay until complete recovery of LH and testosterone secretion [394 ± 65 (3 mg), 484 ± 72 (6 mg) and 668 ± 47 (12 mg) days], and the delay until testes had regrown to normal volume [408 ± 77 (3 mg), 514 ± 74 (6 mg), 676 ± 59 (12 mg) days]. The time taken to restore full ejaculates was also longest for the 12-mg dose: 716 ± 67 (12 mg) days vs 440 ± 66 (3 mg) and 538 ± 83 (6 mg) days after implantation. There was no correlation between delay to recovery of normal ejaculate quality and body mass. We conclude that the dose-response relationship with deslorelin implants is not expressed with respect to the degree of suppression of reproduction, but on the maximum duration of suppression and thus to delay until recovery.
2006
Twenty mature male dogs of mixed breed were randomizeddividedinto five groups of four animals each. Pituitary desensitization was measured by responses to GnRH and LH challenge -test. Group 1(control): dogs received blank implants (placebo) and were injected with GnRH and LH on days 15, 25, 40 and 100 day ( the interval between injection of GnRH and LH was 24 hours). Groups 2 �5 received 6 mg deslorelin implants. Group 2 was given an injection on GnRH on day 15 and bovine LH on day 16 after implantation. Groups 3-5 had similar tests on days 25, 40 and 100 with GnRH and on days 16, 26, 41 and 101 with bovine LH, respectively. The level of LH and testosterone to the GnRH and LH challenge showed significant different between each level of controls and all levels at all days tested in treated dogs (P<0.001). These experiments illustrate that the implantation of GnRH agonist deslorelin as a slow release formulation in dogs, led to desensitization of the pituitary gonadotrophs as well ...
Reproduction in Domestic Animals, 2009
The present study is part of a programme of research designed to evaluate the efficacy of the GnRH superagonist,deslorelin (D-Trp6-Pro9-des-Gly10-LHRH ethylamide), as a contraceptive for male dogs. Adult dogs were assigned to a completely randomized design comprising six groups of four animals. Each dog in the control group received a blank implant (placebo) and each dog in the other five groups received a 6 mg deslorelin implant. One group of deslorelin treated dogs was sacrificed on each of days 16, 26, 41, 101 and 620, and testicular and prostate tissues were collected for study by light and electron microscopy. On days 16 and 26 after implantation, we observed partial disruption of the seminiferous tubules, with early spermatids shed into the lumen. On days 41 and 101 after implantation, 90–100% of the seminiferous tubules were atrophic and aspermatogenic.On day 101 after implantation, 99% of all sections showed atrophy of the epithelium and shrinkage of epithelial height in the ductus epididymides. On days 41 and 101 after implantation, prostate tissue showed complete atrophy of the glandular epithelium (100% of sections) and an apparent increase in the relative proportion of connective tissue. At the electron microscopic level, in dogs treated with deslorelin for 41 and 101 days, the Sertoli cells were smaller and their nucleoli appeared smaller than in the control dogs. The nucleoli of the Leydig cells were atrophied and prostate glandular epithelium showed reduced epithelial height, a trophy of the nucleolus and an absence of secretory granules.Tissues collected during the recovery phase revealed a complete recovery of spermatogenesis. In conclusion, slow release implants containing deslorelin induce a striking a trophy of the testes and prostate gland by 26 days after implantation, explaining the previously reported loss of ejaculate and arrest of sperm output. At histological level,the entire process appears to be completely reversible, in accordance with data on endocrine variables and semen production.
Reproduction, Fertility and Development, 2003
In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin ™ (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.
Reproduction in Domestic Animals, 2012
Stray dogs are a significant problem in large cities. Contraception is an important and useful solution to control the growing population of these dogs. Early-age neutering is an effective technique for canine population control; however, surgical neutering may not be possible in various situations. GnRH-agonist implantation has been successful for long-term reversible contraception in dogs. The efficacy of GnRHagonist implantation on long-term suppression of reproductive performance was observed in male dogs. Eleven 4-month-old dogs were implanted with 4.7, 9.4 mg deslorelin or placebo. Sexual behaviour and testicular size were monitored every 2 months. Ejaculates were collected and evaluated at 8, 12, 15, 18, 24, 30, 32, 34 and 36 months of age. Dogs implanted with placebo were found to be healthy and in normal reproductive status. Most dogs (3/4) implanted with 4.7 mg deslorelin showed male sexual behaviour at age of 34 months old. From this group, two dogs had normal semen quality, while semen could not be collected from the other dog, and after castration, no sperm were obtained following epididymal flushing. One dog implanted 4.7 mg deslorelin and four dogs implanted with 9.4 mg deslorelin remained in the non-pubertal reproductive status at 30-34 months. The delay to puberty was longer in dogs implanted with higher dose of GnRH agonist. Implantation of pre-pubertal dogs with high doses of GnRH agonist will delay the onset of puberty and may be an effective strategy to reduce the number of unwanted breedings.
Journal of andrology
The objective of this study was to determine if prolonged pulsatile administration of homologous gonadotropin-releasing hormone (GnRH) at therapeutic or 5x therapeutic doses would cause down-regulation of the stallion's hypothalamic-pituitary-testicular axis. Fifteen stallions were randomly assigned to three treatment groups (n=5/group) and received a 0.5 ml subcutaneous dose of saline (group 1), 50 microg GnRH (group 2), or 250 microg GnRH (group 3) every 2 hours for 75 days. Weekly evaluations of follicle stimulating hormone, luteinizing hormone, and testosterone and monthly evaluations of daily sperm output and spermatozoal motility failed to demonstrate any decreased pituitary or gonadal responsiveness within or among treatment groups (P > 0.1) as a result of treatment with GnRH. Results of this study demonstrate that the hypothalamic-pituitary-testicularaxis of the stallion, unlike that of other domestic species, is remarkably refractory to GnRH-induced down-regulation.
261 FERTILITY CONTROL BY GnRH ANALOGUES IN DOGS
Reproduction, Fertility and Development
GnRH plays a pivotal role in reproduction by stimulating the release of gonadotrophins. Chemical substitutions in the GnRH molecule lead to analogues possessing antagonist or agonist activity (Paramo RM et al. 1993 J. Reprod. Fertil. Suppl. 47, 387–397). The highly potent agonist analogue, Buserelin, with up to 20 times of potency, by increasing binding affinity, desensitizing competitive receptors, and resisting metabolic degradation, shuts down rather than stimulates reproductive function (Bertschinger HJ et al. 2001 J. Reprod. Fertil. Suppl. 57, 275–283). In man, Buserelin is employed in several gonadal hormone-dependent diseases and for prostatic cancers. We suppress gonadal function in male dogs using Buserelin. Eight intact male German sheep dogs 20 months old were divided into two groups; A, 4 subjects treated for pharmacological castration (Buserelin acetate, 0.3 mg/each, s.c., every 8 h for 30 days) (Suprefact-Aventis Pharma, Italy); B, 4 subjects treated with placebo (NaCl...
Reproduction, 2003
Administration of GnRH agonist for an extended period inhibits pulsatile LH release but enhances testicular function of bulls. The mechanism whereby long-term administration of GnRH agonist enhances testosterone concentration in the blood of bulls has not been determined. The aim of this study was to determine whether chronic treatment with the GnRH agonist, azagly-nafarelin, increases blood concentrations of LH and FSH in prepubertal bulls. Two different doses of the GnRH agonist were administered via Alzet mini-osmotic pumps for 28 days. Blood samples were collected at 20 min intervals for 24 h at days 2, 13 and 25 of treatment. Agonist-treated groups had reduced testosterone pulse frequency (P < 0.05) and increased mean and basal concentrations of testosterone (P < 0.05) compared with untreated control bulls. Basal LH concentrations were higher in agonist-treated bulls during all three periods (P < 0.05) and overall (1 ng ml −1 higher, compared with control bulls; P < 0.001). Frequency of LH pulses in the agonist-treated groups was reduced to less than one pulse in 24 h. Agonist-treated bulls tended to have (P < 0.10) or had (P < 0.05) a slight but significant increase in blood FSH concentration. In conclusion, the higher blood testosterone concentration in bulls after prolonged treatment with GnRH agonist may result, at least in part, from changes in the testes induced by enhanced basal concentration of LH.
Theriogenology, 2020
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Animal reproduction science, 2018
The hypothesis in this study was continuous treatment of stallions with the GnRH agonist deslorelin inhibits reproductive functions. A 2-week pre-experimental period was followed by an 11-week deslorelin implant treatment. Stallions received 4.7 (D1, n = 7), or 18.8 mg deslorelin (D2, n = 5) or remained untreated (C, n = 5). Libido, sperm motility, membrane integrity, DNA fragmentation, estrogen receptors, basal plasma testosterone and Anti Muellerian hormone (AMH) concentrations were evaluated once weekly during the treatment period. The testosterone response to the GnRH agonist buserelin and hCG was evaluated twice. In Week 2, stallions in Group C but not Groups D1 and D2 responded to buserelin with testosterone release (P < 0.001), while in Week 9, stallions in Group C and D1 but not D2 released testosterone after buserelin administration (group P < 0.01, week P = 0.01). Stallions of all groups responded to hCG with testosterone release at both times of hCG administration (...