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

本实验观察了促性腺激素释放激素激动剂（GnRH-A）缓释制剂对犬生殖功能的抑制作用，结果如下：1.本文报道了一种灵敏、特异的单克隆抗体酶免疫测定法。结果表明，雄犬下丘脑GnRH水平随年龄的增长而升高，至4月龄时升高，6月龄至2岁时下降至平台期。对5只成年雄性狗静脉注射合成的GnRH后，血浆水平下降50%所需的时间为2.2（± SY）。[)0.1（SEM）最小值2.睾丸促黄体生成激素（LH）受体的发育与睾丸生长和血浆雄激素的增加是一致的。性腺对LH敏感性的增加可能是公犬青春期雄激素分泌显著增加的原因.单次注射GnRH-A缓释制剂（1 mg肽/kg）可抑制雄性犬的垂体-睾丸功能。治疗后4个月，观察到完全恢复正常的精子发生。当暴露于GnRH（10 nM）的4小时连续输注时，在体外灌流实验中观察到垂体去敏，表明药物的长效效力可能是抑制垂体和睾丸功能的原因.在母犬产后4个月内开始多次注射GnRH-A缓释制剂（1 mg肽/kg，每3个月一次）9个月期间，未检测到新的发情。相反，在产后5个月时对母犬单次注射GnRH-A缓释制剂（0.1 mg肽/kg）导致诱导发热：母犬在这些时间交配并产生正常窝仔。

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.