LHRH and analogs: reproductive pharmacology and contraceptive and therapeutic utility.
LHRH and analogs: reproductive pharmacology and contraceptive and therapeutic utility.
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LHRH 和类似物：生殖药理学以及避孕和治疗用途。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
A. Corbin
中科院分区：
文献类型：
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作者：
Bex Fj;A. Corbin
在过去的十年中，促黄体生成激素释放激素（LHRH）及其类似物的化学和药理学的发展取得了革命性的进展，这极大地增强了对LHRH在控制两种垂体促性腺激素卵泡刺激素（FSH）和促黄体生成素（LH）分泌中的主要作用的理解。本讨论审查：LHRH的基本原则; LHRH对垂体促性腺激素功能的调节;受孕方面（用LHRH和LHRH激动剂诊断治疗女性和男性不育症）; LHRH拮抗剂--避孕和治疗方面（化学开发LHRH拮抗剂的作用机制LHRH拮抗剂的生殖效应）; LHRH和LHRH激动剂--女性避孕和治疗方面（对雌性动物的抗生育作用对雌性动物的抗生育作用机制对女性的治疗效用）; LHRH和LHRH激动剂--男性避孕和治疗方面（雄性动物的抗生育作用、雄性避孕药的抗生育作用机制和男性的治疗效用）;以及安全性和可逆性研究-辅助药理学、毒理学和代谢评价。由于其竞争性抑制LHRH的能力，拮抗剂作为排卵抑制剂受到关注。相比之下，具有更复杂的生殖药理学特征的“超级”激动剂已被研究其在生殖功能减退状态下的促生育（受孕）潜力，并且更广泛地研究其矛盾的避孕承诺。动物和临床研究表明，这些激素能抑制女性和男性的生殖过程，如促性腺激素分泌过多、垂体脱敏、排卵抑制、性腺下调、类固醇生成抑制、黄体溶解、干扰发情和月经周期、月经初潮、妊娠终止、青春期延迟和生精抑制。在动物和临床安全性研究中，已观察到激动剂在有效剂量下耐受性良好且无不良副作用。最近的临床研究采用慢性鼻腔给药的激动剂，以女性加强继续支持这种新的避孕方法。在人类男性中，激动剂可以严重延迟或停止精子发生，但它们也会引起睾酮下降和性欲丧失的不可接受的副作用。基于LHRH类似物，特别是激动剂抑制类固醇依赖性肿瘤生长的能力，抑制性类固醇降低特性的应用已经扩展到癌症治疗。
In the past decade there have been revolutionary advances in the development of the chemistry and pharmacology of luteinizing hormone-releasing hormone (LHRH) and its analogs which have greatly enhanced understanding of the primary role of LHRH in controlling the secretion of the 2 pituitary gonadotropic hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH). this discussion examines: the basic principles of LHRH; LHRH regulation of pituitary gonadotropic function; conceptive aspects (diagnostic treatment of female and male infertility with LHRH and LHRH agonists); LHRH antagonists -- contraceptive and therapeutic aspects (chemical development LHRH antagonist mechanism of action the reproductive effects of LHRH antagonists); LHRH and LHRH agonists -- contraceptive and therapeutic aspects in the female (antifertility effects in female animals antifertility mechanism of action in the female therapeutic utility in women); LHRH and LHRH agonists -- contraceptive and therapeutic aspects in the male (antifertility effects in male animals antifertility mechanism of action in the male contraceptive and therapeutic utility in men); and safety and reversibility studies -- ancillary pharmacology toxicologic and metabolic evaluation. The antagonists by virtue of their ability to inhibit LHRH competitively have received attention as ovulation inhibitors. by contrast the "super" agonists which possess a more complex reproductive pharmacologic profile have been studied for their profertility (conceptive) potential in hyporeproductive states and more extensively for their paradoxical contraceptive promises. Animal and clinical studies demonstrate that these agnosits can inhibit reproductive processes in females and males as evidenced by gonadotropin hypersecretion pituitary desensitization ovulation inhibition gonadal downregulation steroidogenic inhibition luteolysis interference with estrous and menstrual cycles early onset of menses pregnancy termination retardation of puberty ans spermatogenic inhibition. In animal and clinical safety studies the agonists have been observed to be well tolerated and free of untoward side effects at efficacious doses. Recent clinical studies employing chronic nasal delivery of the agonists to females reinforced continued support of this novel approach to contraception. In human males the agonists can severely retard or halt spermatogenesis but they also cause the unacceptable side effects of testosterone decline and libidinal loss. Use of the inhibitory steroid lowering properties has been extended to cancer therapy based on the ability of the LHRH analogs particularly the agonists to inhibit the growth of steroid dependent tumors.