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

促性腺激素释放激素激动剂缓释制剂对狗生殖功能的抑制作用

基本信息

批准号：
03454112
负责人：
MORI Junichi
金额：
$ 2.11万
依托单位：
University of Osaka Prefecture
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

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.

检测了促性腺激素释放激素激动剂（GnRH-A）缓释制剂对狗生殖功能的抑制作用，得到了以下结果。 1．采用酶联免疫法测定GnRH。该方法已成功应用于下丘脑和血浆 GnRH 的分析。在雄性狗中，下丘脑 GnRH 水平随着年龄的增长而增加，直至 4 个月，然后下降。 5 只成年雄性狗静脉注射合成 GnRH 后血浆水平从 6 个月到 2 年达到稳定水平所需的时间为 2.2(]SY.+-.[)0.1 (SEM) min.2。狗体内睾丸黄体生成素 (LH) 受体的发育与睾丸生长和血浆雄激素的增加同时发生。性腺对 LH 敏感性的增加可能与此有关。导致雄性狗青春期雄激素分泌显着增加。3.单次注射GnRH-A缓释制剂(1mg肽/kg)可以抑制雄性狗的垂体-睾丸功能。治疗四个月后，当连续输注 GnRH (10 nM) 4 小时时，在体外灌注中观察到垂体脱敏。实验表明，该药物的长效作用可能是抑制垂体和睾丸功能的原因。 4．在9个月的多次注射GnRH-A缓释制剂（1 mg肽//）的治疗过程中。母犬产后4个月内开始，没有检测到新的发情，相反，单次注射GnRH-A缓释制剂（0.1毫克肽/公斤）。母犬产后 5 个月会出现诱导发情：母犬在这段时间内交配并产下正常的幼仔。