Acute follicular response to FSH in heifers downregulated long term with a GnRH agonist and with suppressed ovarian follicular growth.

The objectives of this study were to (1) ascertain ovarian follicular status in heifers where the pituitary gonadotrope cells producing LH and FSH were downregulated by long-term treatment with a GnRH agonist and (2) characterize the acute superstimulation of follicular growth in response to FSH in heifers where the pituitary was downregulated with a GnRH agonist. At the start of the study, heifers (3 year old) were implanted with GnRH agonist (n = 20) or received no treatment (control, n = 5). After 6 months, follicular growth in heifers implanted with GnRH agonist was restricted to early antral follicles (2-4 mm). At this time, these heifers were allocated to four groups and follicular development was superstimulated with FSH as follows: group 1 (n = 5) and group 2 (n = 5), a conventional FSH protocol with injections over 4 days (Days 0-3) with Group 2 receiving two times the normal dose of FSH; group 3 (n = 5), a single injection of FSH in saline on Day 0; group 4 (n = 5), a single injection of FSH in slow-release polyvinylpyrrolidone on Day 0. Follicular growth in the control heifers (n = 5) was superstimulated using the conventional 4-day FSH protocol. On Day 5, heifers in groups 1 and 2 had similar (P > 0.05) numbers of follicles in the size categories 6 to 7 mm (12.8 ± 3.0 follicles) and 8 to 9 mm (6.5 ± 1.0) as control heifers (6-7 mm, 14.6 ± 2.2; 8-9 mm, 6.2 ± 2.2) and six of the former heifers had follicles 10 mm (3.2 ± 1.4). Also on Day 5, follicular growth for heifers in group 3 was restricted to 4 to 5 mm (11.6 ± 3.0) and 6 to 7 mm (7.6 ± 3.7), whereas four out of five heifers in group 4 had follicles of 6 to 7 mm (8.2 ± 2.3) and three heifers had follicles of 8 to 9 mm (4.6 ± 2.2) and 10 mm (2.2 ± 0.9). Injection of exogenous LH on Day 5 induced ovulation in 9 out of 10 heifers in groups 1 and 2, no heifers in group 3, and 2 of 5 heifers in group 4. Plasma concentrations of progesterone 6 days after ovulation were the same (P > 0.05) for heifers in groups 1 and 2 (8.9 ± 0.9 ng/mL) and control heifers (10.0 ± 0.9 ng/mL). This study has shown that heifers treated chronically with a GnRH agonist have suppressed ovarian follicular growth but are able to respond to acute superstimulation with FSH. Furthermore, follicles in heifers treated with a GnRH agonist undergo morphologically normal growth in response to FSH and can ovulate and develop into a CL. The long-term GnRH agonist-treated heifer provides a practical model for repeated ovarian follicular superstimulation, multiple ovulation, and embryo transfer, without the need to control stage of the estrous cycle.

Chronic treatment of female tammar wallabies with deslorelin implants during pouch life: effects on reproductive maturation.

The present study reports on attempts to delay puberty in a model marsupial species using the gonadotrophin-releasing hormone (GnRH) agonist deslorelin. Female tammar wallaby pouch young received deslorelin (5 mg) or placebo implants (n=8/group) when they were 193±2 days old. Sexual maturity was significantly delayed in deslorelin-treated animals, with the first successful production of offspring in treated and control animals occurring at 813±62 and 430±42 days of age, respectively. This delay was associated with a period of retarded pouch and teat development. Progesterone concentrations remained at basal levels throughout the first breeding season, indicating the absence of luteal cycles in treated females. Recovery and maturation of the hypothalamic-pituitary axis was a gradual process. Treated animals failed to respond to GnRH challenge at 12 months of age and had a reduced LH response at 18 months of age, before attaining full responsiveness by 24 months of age. Despite this apparent pituitary recovery by 24 months of age, as evidenced by complete teat eversion and LH responsiveness to GnRH, the time to first parturition was significantly delayed beyond this time in three females. This suggests that there may be longer-lasting effects at the level of the ovary and/or on FSH secretion. The significant delay in the onset of sexual maturation in response to chronic GnRH agonist treatment in this model marsupial species may be of practical significance to the management of fertility in captive and semi-free range marsupial populations.

Delay of puberty and reproductive performance in male dogs following the implantation of 4.7 and 9.4 mg GnRH-agonist deslorelin at an early pre-pubertal age.

CONTENTS: 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 GnRH-agonist 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.

Dose-response studies for pituitary and testicular function in male dogs treated with the GnRH superagonist, deslorelin.

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-Trp6-Pro9-des-Gly10-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 dose-response 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.

Morphological study of the effects of the GnRH superagonist deslorelin on the canine testis and prostate gland.

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, 90­100% 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.

Use of a gonadotropin releasing hormone agonist implant as an alternative for surgical castration in male ferrets (Mustela putorius furo).

Surgical castration in ferrets has been implicated as an etiological factor in the development of hyperadrenocorticism in this species due to a castration-related increase in plasma gonadotropins. In search for a suitable alternative, the effect of treatment with the depot GnRH-agonist implant, deslorelin, on plasma testosterone concentrations and concurrent testes size, spermatogenesis, and the typical musky odor of intact male ferrets was investigated. Twenty-one male ferrets, equally divided into three groups, were either surgically castrated, received a slow release deslorelin implant or received a placebo implant. Plasma FSH and testosterone concentrations, testis size and spermatogenesis were all suppressed after the use of the deslorelin implant. The musky odor in the ferrets which had received a deslorelin implant was less compared to the ferrets which were either surgically castrated or had received a placebo implant. These results indicate that the deslorelin implant effectively prevents reproduction and the musky odor of intact male ferrets and is therefore considered a suitable alternative for surgical castration in these animals.

Pituitary and testicular endocrine responses to exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone in male dogs treated with GnRH agonist implants.

The present study tested whether exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) can stimulate LH and testosterone secretion in dogs chronically treated with a GnRH superagonist. Twenty male adult dogs were assigned to a completely randomised design comprising five groups of four animals. Each dog in the control group received a blank implant (placebo) and each dog in the other four groups received a 6-mg implant containing a slow-release formulation of deslorelin (d-Trp6-Pro9-des-Gly10-LH-releasing hormone ethylamide). The same four control dogs were used for all hormonal challenges, whereas a different deslorelin-implanted group was used for each challenge. Native GnRH (5 microg kg(-1) bodyweight, i.v.) was injected on Days 15, 25, 40 and 100 after implantation, whereas bovine LH (0.5 microg kg(-1) bodyweight, i.v.) was injected on Days 16, 26, 41 and 101. On all occasions after Day 25-26 postimplantation, exogenous GnRH and LH elicited higher plasma concentrations of LH and testosterone in control than deslorelin-treated animals (P < 0.05). It was concluded that, in male dogs, implantation of a GnRH superagonist desensitised the pituitary gonadotrophs to GnRH and also led to a desensitisation of the Leydig cells to LH. This explains, at least in part, the profound reduction in the production of androgen and spermatozoa in deslorelin-treated male dogs.

Chronic treatment of male tammar wallabies with deslorelin implants during pouch life: effects on development, puberty, and reproduction in adulthood.

The present study evaluated the effects of chronic GnRH agonist (deslorelin) treatment on sexual maturation in the male tammar wallaby. Slow-release deslorelin or placebo implants were administered to male pouch young (n = 10/group) when they were between 180 and 200 days old, to determine if disruption of the pituitary-testicular axis during development altered the timing of sexual maturation or had long-term effects on adult reproductive function. Deslorelin treatment caused retardation of testicular growth and reduced the serum FSH and testosterone concentrations between 12 and 24 mo of age. Maturation of the hypothalamic-pituitary-testicular axis was also delayed in treated animals at 13 and 19 mo of age. Despite these alterations in the pattern and timing of neuroendocrine development, sexual maturation was not permanently blocked in these animals and deslorelin-treated animals reached sexual maturity at the same age as treated animals, as evidenced by a fully functional pituitary-testicular axis and proven fertility at 25 mo of age. The ability of the treated animals to reach puberty at the same time as control animals, despite delayed maturation of the hypothalamic-pituitary-testicular axis, suggests that puberty in the male tammar wallaby is additionally regulated by other, gonadotropin-independent factors.

A review of advances in the use of the GnRH agonist deslorelin in control of reproduction.

The prevention of breeding in animals using GnRH analogues has been the object of research over many years. Recently, a new drug delivery formulation was developed which enabled the development of products that could be commercialised for veterinary use. The formulation has now been approved in certain countries for use in male dogs, and applications are being expanded to cover repeat usage, extended duration, use in females, other indications and other animal species. With respect to repeat usage, dogs have been re-implanted for four consecutive doses and monitored until they returned to normal steroidogenesis. All dogs returned to normal steroidogenesis following cessation of treatment. In females, it was previously shown that implanted bitches with progesterone < 5 ng/mL at the time of implantation had an induced estrus. In a new study at Chulalongkorn University, implanting female pups at around 4 mo prevented this occurrence, whereas implantation at 7 mo did not.

Short-term progestin treatments prevent estrous induction by a GnRH agonist implant in anestrous bitches.

The objective of this study was to test the efficacy and safety of a short-term progestin treatment administered at two different times to prevent estrous induction in response to the administration of an implant releasing the GnRH agonist, deslorelin acetate (DA), in anestrous bitches. Interestrous intervals (IEI) observed prior to and post DA were compared. Forty-two anestrous bitches, with previous IEI history, were randomly allocated to one of the following treatments: PL: placebo sc (n = 12); MA: megestrol acetate 2mg/kg po for 8 days (n = 4); DA: 10mg sc (n = 8); MA&DA-1: MA beginning the day before DA (n = 8); and MA&DA-4: MA beginning 4 days before DA (n = 10). The dose of MA was identical for each treatment. All bitches were examined daily for 1 month and then every 3 months until the next spontaneous post-treatment estrous cycle. Post-GnRH estrous response occurred in 0, 0, 100, 50, and 10% of the PL, MA, DA, MA&DA-1, MA&DA-4, groups, respectively (<0.01). There was an interaction between the treatment and period for the duration of the IEI (< 0.01). Changes in IEI were different among treatments (p<0.01); the three DA-treated groups (147.5% +/- 10.3, 161.3% +/- 14.1, 148.6% +/- 19.2) differed from both the MA (12.9% +/- 17.6) and PL (8.1% +/- 7.8), but not among themselves. It is concluded that an 8 days megestrol protocol and DA on Day 4 was better than DA on Day 1 to prevent estrous response in anestrous bitches and that both protocols significantly increased the IEI.

Applications of GnRH in the control and management of fertility in female animals.

Gonadotropin releasing hormone (GnRH) has long been recognized as a potential target for the control and management of fertility in female animals. Attempts to apply GnRH-based technology to manage fertility have focussed on the development of GnRH agonists, antagonists and vaccines. All of these methods have potential, but the widespread application of these technologies has been limited to date. The greatest advance in the use of GnRH-based technology for long-term fertility control in recent years has been the development and commercialization of depot formulations that release GnRH agonists for periods of up to 1 year. These products have a broad range of potential applications in production and domestic animal management. The further development and commercialization of GnRH vaccines has been hampered by the variability of response between individual animals. The need to use adjuvant and multiple boosters also make this a less attractive option than the current GnRH agonist technology. However, GnRH vaccines have the advantage that they do not induce the initial stimulatory response that follows GnRH agonist administration. GnRH antagonists and GnRH-toxin conjugates show promise but are in an earlier phase of development. To date, no depot or long-acting formulations of antagonists have been developed. GnRH-toxin conjugates have yet to achieve permanent sterilization, but further dose-response trials may advance this approach.

Long-term effects of deslorelin implants on reproduction in the female tammar wallaby (Macropus eugenii).

The contraceptive and endocrine effects of long-term treatment with implants containing the GnRH agonist deslorelin were investigated in female tammar wallabies (Macropus eugenii). Fertility was successfully inhibited for 515 +/- 87 days after treatment with a 5 mg deslorelin implant (n = 7), while control animals gave birth to their first young 159 +/- 47 days after placebo implant administration (n = 8). The duration of contraception was highly variable, ranging from 344 to 761 days. The strict reproductive seasonality in the tammar wallaby was maintained once the implant had expired. This inhibition of reproduction was associated with a significant reduction in basal LH concentrations and a cessation of oestrous cycles, as evidenced by low progesterone concentrations. There was evidence to suggest that some aspect of either blastocyst survival, luteal reactivation, pregnancy or birth may be affected by deslorelin treatment in some animals. These results show that long-term inhibition of fertility in the female tammar wallaby is possible using slow-release deslorelin implants. The effects of deslorelin treatment were fully reversible and there was no evidence of negative side effects. Slow-release GnRH agonist implants may represent a practicable method for reproductive management of captive and semi-wild populations of marsupials.

Effect of deslorelin implants on follicular development, parturition and post-partum oestrus in the tammar wallaby (Macropus eugenii).

The effect of treatment with slow release implants containing the GnRH agonist, deslorelin, was investigated in female tammar wallabies. Pouch young were removed from 16 wallabies presumed to be carrying quiescent blastocysts. Eight received a 5 mg deslorelin implant and eight received a placebo implant. Animals were caught daily from day 25 to day 30 and their pouches inspected for newborn young and their urogenital sinus checked for a copulatory plug. Treatment with deslorelin did not affect reactivation of a dormant blastocyst and subsequent birth in 4/8 animals, but post-partum mating was inhibited in these animals. Five control and five treated animals were killed within 0-48 h post partum and their reproductive tracts analysed. At autopsy, all five control animals had large preovulatory follicles but only one deslorelin-treated animal showed signs of follicular development. These differences were also reflected in the weights of the lateral vaginae, with treated animals showing no evidence of oestrogenic stimulation. The remaining three control and three treated animals were monitored for approximately 2 years. The long-term contraceptive effects of a single 5 mg deslorelin implant lasted for just under one year. These results indicate that slow release deslorelin implants inhibit follicular development in the female tammar wallaby for extended periods of time and may have potential application in reproductive management of captive marsupials in the kangaroo family.

Effects of a gonadotropin-releasing hormone agonist implant on reproduction in a male marsupial, Macropus eugenii.

This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P < 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P > 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.

The effect of GnRH analogs on urinary incontinence after ablation of the ovaries in dogs.

After removal of the ovaries approximately 20% of dogs develop urinary incontinence. Removal of the gonads results in estrogen deficiency and chronic elevation in the production and secretion of FSH and LH. The gonadotrophins may directly or indirectly, adversely affect the sphincter function of the urethra. Estrogen replacement therapy and treatment with sympathomimetics, such as ephedrine or phenylpropanolamine (PPA), are effective only in some of the affected dogs, and many of these subsequently become nonresponsive. Since the role of the elevated gonadotrophins has not been elucidated, we used depot preparations of GnRH analogues to down-regulate gonadotrophins once or twice in 13 ovariectomized (ovx), incontinent dogs, which were either refractory to alpha-adrenergics (n=11) or in which alpha-adrenergics were contraindicated (n=2). Dogs were treated with leuprolide, deslorelin, buserelin or triptorelin. In 7 dogs treatments with GnRH analogues alone (n=11) resulted in continence for 50-738 days (mean 247). In all dogs except one, where GnRH treatments did not resolve the incontinence completely, additional treatment with phenylpropanolamine was successful. With additional treatment of phenylpropanolamine complete continence was restored for 21-367 days (mean 159). All treatments caused long-term reduction of circulating FSH and LH concentrations to very low or undetectable levels. No adverse effects of treatments were observed.

Pituitary expression of LHbeta- and FSHbeta-subunit mRNA, cellular distribution of LHbeta-subunit mRNA and LH and FSH synthesis during and after treatment with a gonadotrophin-releasing hormone agonist in heifers.

The aim was to examine transcriptional and post-transcriptional regulation of LH and FSH biosynthesis. Female cattle were allocated to three groups: (i) Group 1, control (n = 6), synchronized to be at around Day 11 of the oestrous cycle on Day 31; (ii) Group 2 (n = 6), treated with gonadotrophin-releasing hormone (GnRH) agonist (deslorelin) for 31 days; and (iii) Group 3 (n = 6), treated with deslorelin for 28 days. All animals were slaughtered on Day 31. For animals in Group 2, pituitary content of LHbeta-subunit mRNA was suppressed 60% (P < 0.001) and LH 95% (P < 0.001), whereas FSHbeta-subunit mRNA was suppressed 25% (P > 0.05) and FSH 90% (P < 0.001). Three days after treatment with deslorelin (Group 3) LHbeta-subunit mRNA and LH remained suppressed (50% and 95%, respectively; P < 0.001). At the same time, FSHbeta-subunit mRNA did not differ from controls (P > 0.05) whereas FSH remained reduced by 80% (P < 0.001). The ratio of LHbeta-subunit mRNA present in the nucleus versus cytoplasm of gonadotroph cells was reduced (P < 0.05) in heifers during treatment with deslorelin (0.59 +/- 0.05) compared with the ratio in control heifers (1.31 +/- 0.22) and heifers 3 days after discontinuation of treatment (1.01 +/- 0.05). The findings indicated that treatment with GnRH agonist can suppress LHbeta-subunit mRNA expression without any significant effect on FSHbeta-subunit mRNA. As LH and FSH contents were suppressed to a greater degree than their beta-subunit mRNAs, it would appear that treatment with a GnRH agonist might influence gonadotrophin biosynthesis by a post-transcriptional mechanism(s). For LHbeta-subunit mRNA, this would appear not to be reduced export of message from the nucleus.

Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs.

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM) (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.

Induction of contraception in some African wild carnivores by downregulation of LH and FSH secretion using the GnRH analogue deslorelin.

The GnRH analogue deslorelin, in long-acting biocompatible implants, was used as a contraceptive in 31 cheetahs (13 females and 18 males), 21 African wild dogs (15 females and 6 males), 10 lionesses and four leopards (three females and one male). A dose of 12 or 15 mg deslorelin was administered to lions, whereas 6 mg deslorelin was administered to the other species. Monitoring consisted of observations, measurement of plasma progesterone and testosterone concentrations, vaginal cytology and evaluation of semen and sex organs. Deslorelin induced contraception in lionesses for 12-18 months, and in female cheetahs and leopards for a minimum of 12 months after treatment. Two male cheetahs had no viable spermatozoa or detectable plasma testosterone 21 months after treatment with deslorelin. Female wild dogs responded less consistently and one bitch conceived 4 weeks after implantation. However, in nine bitches, mating could be postponed until the next breeding season. Male dogs responded consistently and the contraception was effective for approximately 12 months. Although lionesses and cheetahs may become attractive to males for a few days after treatment, mating was not observed. No side-effects or behavioural changes were noted, indicating that deslorelin is a safe drug to use for the contraception of the species described. Males remain fertile for the first 6 weeks after the insertion of implants and should be separated from cyclic females during this period.

Sustained testicular atrophy in bulls actively immunized against GnRH: potential to control carcase characteristics.

The objectives were to determine whether active immunization against gonadotrophin releasing hormone (GnRH) induced a long-term suppression of testicular function in bulls, and to ascertain the effects of immunization against GnRH on carcase and meat quality characteristics. In experiment 1, 6-month-old Zebu bulls were assigned to: control (n=25), no treatment; immunized (n=31), immunized against GnRH at 0 and 4 months (anti-GnRH(2)), with a sub-set of bulls (n=17) immunized again at 10 months (anti-GnRH(3)). After the second immunization, testicular growth ceased for 2 months in 14/31 (45%) bulls and for at least 6 months in 17/31 (55%) bulls. Among the latter bulls (anti-GnRH(3)) the testes did not grow for >1 year after the third immunization in 5/17 (30%) bulls. In experiment 2, 22-month-old Zebu bulls were assigned to: control (n=14), no treatment; immunized (n=17), immunized against GnRH at 0, 2 and 4 weeks. The testes decreased (P<0.05) in size for 2 months after immunization in 11/17 (65%) bulls and then re-initiated growth, whilst in 6/17 (35%) bulls the testes continued to decrease in size for 4 months and did not re-initiate growth for 1 year. At slaughter, the latter immunocastrated bulls had carcase and meat quality characteristics the same as contemporary bulls that had been castrated before puberty. The findings demonstrated that active immunization against GnRH can induce a long-term suppression of testicular function in a proportion of bulls. Also, when bulls are immunocastrated after puberty, carcase and meat quality traits change from those typical of entire bulls to traits that are characteristic of long-term castrated bulls.

Suppression of the oestrous responses of bitches to the GnRH analogue deslorelin by progestin.

Studies were undertaken in Australia and Belgium to determine whether the initial pro-oestrous-oestrous responses of anoestrous bitches to treatment with deslorelin administered in a s.c. implant were inhibited by progestin treatment. Thirty-nine bitches of mixed breeding were treated daily with 2 mg megestrol acetate kg-1 body weight for 21 (group 1, n = 5) or 14 days (group 2, n = 10), or with 1 mg megestrol acetate kg-1 body weight for 14 days (group 3, n = 10). A deslorelin (6 mg) implant was placed s.c. on day 14 (group 1) or day 7 (groups 2 and 3) of treatment. Bitches not treated with progestin also received a deslorelin implant (group 4, n = 9) or were untreated controls (group 5, n = 9). Signs of pro-oestrus-oestrus were not observed in bitches in groups 1, 2 and 5, but were observed in bitches in groups 3 (4/10) and 4 (9/9). Four bitches in group 4 were mated, two of which became pregnant. The pregnancies failed at about day 40 of gestation and were associated with low plasma progesterone concentrations. Treatment with progestin inhibited the pro-oestrous-oestrous responses of bitches to deslorelin.