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.

检查了促性腺营养蛋白释放的马酮激动剂（GnRH-A）对狗中生殖功能的持续释放公式的抑制作用，并获得了以下结果。1。已经开发了使用单克隆抗体测定GNRH的敏感且特异性的酶免疫测定。该方法已成功地用于分析男性狗的下丘脑和血浆gnrh.in，下丘脑GnRH水平随着年龄的年龄长达4个月而增加，然后从6个月到2岁降至高原。在静脉注射GNRH对5个成年男性狗的静脉内服用后，血浆水平降低50％所需的时间为2.2（]SY。+ - 。[）0.1（sem）min.2。狗在狗中的测定叶酸马酮（LH）受体的发育与实验生长和血浆雄激素的增加相吻合。性腺对LH的敏感性的增加可能是可以重新降低的，因为雄性狗在青春期期间发生的雄激素的秘密增加了。3。单一注入GnRH-A（1 mg胡椒/kg）的持续释放公式可以抑制雄性狗的垂体检测功能。治疗后四个月，观察到正常的精子发生。当暴露于4-H连续输注GnRH（10 nm）时，在体外炎性实验中观察到了垂体信念，这表明该药物的长效效力可能是抑制垂体和证明功能的原因。4。在9个月的治疗中，多次注射持续释放的GnRH-A（1 mg胡椒/kg，每3个月一次），从母狗产后4个月内开始，未检测到新的发情。形成鲜明对比的是，在产后5个月时，单次注射GnRH-A（0.1 mg辣椒/千克）的持续释放式公式导致了诱发的热量：当时的bit子伴侣并产生了正常的ilters。