Inhibitory Effects of a Sustained Release Formulation of the Gonadotrophin-Releasing Hormone Agonist on Reproductive Function in the Dog

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Inhibitory effects of a sustained release formulation of the gonadotrophin-releasing hormone agonist (GnRH-A) on reproductive function in the dog were examined, and the following results were obtained.1. A Sensitive and specific enzyme immunoassay for the determination of GnRH using a monoclonal antibody has been developed. This method was successfully applied for analysis of hypothalamic and plasma GnRH.In male dogs, hypothalamic GnRH levels increased with age up to 4 months, then fell to a plateau from 6 months to 2 years. The time required for a 50% reduction in plasma levels following intravenous administation of synthetic GnRH to 5 adult male dogs was 2.2(]SY.+-。[)0.1 (SEM) min.2. The development of testicular luteinizing hormone (LH) receptors in the dog was coincident with the increase in testicular growth and plasma androgens. The increase in gonadal sensitivity to LH could be reponsible for the marked increase in secretion of androgen which occurs during puberty in the male dog.3. A single injection of sustained-release formulation of GnRH-A (1 mg peptide/kg) could inhibit pituitary-testicular function in the male dog. Four months after the treatment, a complete return to normal spermatogenesis was observed. When exposed to a 4-h continuous infusion of GnRH (10 nM), pituitary desnsitization was observed in in vitro perifusion experiments, suggesting that the long-acting potency of the drug could be the reason for the inhibition of the pituitary and testicular function.4. During 9 months of treatment with multiple injections of sustained-release formulation of GnRH-A (1 mg peptide/kg, once every 3 months), starting within 4 months postpartum in bitches, no new oestrus was detected. On the contrary, a single injection of sustained-release formulation of GnRH-A (0.1 mg peptide/kg) at 5 months postpartum in bitches resulted in an induced heat : the bitches mated at those time and produced normal litters.