Schally Andrew V, González Bárcena David
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, Miami, FL, USA.
Gac Med Mex. 2006 Jul-Aug;142(4):315-25.
Early clinical trials in Mexico with analogs of luteinizing hormone-releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Extensive clinical studies were carried out at IMSS with agonists of LH-RH, both in men and woman. All subjects responded to LH-RH agonists with a release of LH and FSH, but repeated administration of these analogs, initially aimed at stimulation of fertility (thought to stimulate fertility), was later shown to result in inhibition due to desensitization of pituitary gland and downregulation of LH-RH receptors. Various clinical investigations with LH-RH antagonists were also carried out. This included the first demonstration that LH-RHantagonists can suppress LH and FSH and sex steroid secretion in men and women. Various studies in Mexico with early LH-RH antagonists aimed at the development of new contraceptive methods were reviewed. Modern LH-RH antagonist Cetrorelix was shown to be effective in men and women and useful in treatment of uterine leiomyomas and benign prostatic hyperplasia. Major oncological studies were also carried out with agonist D-Trp6-LH-RH and antagonist Cetrorelix in men with prostate cancer, which demonstrated therapeutic efficacy of both types of analogs. Some endocrine studies with early analogs of somatostatin were also cited and a clinical trial with somatostatin analog vapreotide in patients with relapsed prostate cancer was reviewed. All these studies played a major role in introducing analogs of hypothalamic-releasing hormones into clinical medicine.
对墨西哥早期使用促黄体生成激素释放激素(LH-RH,也称为促性腺激素释放激素Gn-RH)类似物的临床试验进行了综述。墨西哥社会保障局(IMSS)对LH-RH激动剂在男性和女性中都开展了广泛的临床研究。所有受试者对LH-RH激动剂的反应都是释放促黄体生成素(LH)和促卵泡生成素(FSH),但这些类似物的反复给药,最初旨在刺激生育能力(原以为能刺激生育),后来发现由于垂体脱敏和LH-RH受体下调而导致抑制作用。还开展了各种使用LH-RH拮抗剂的临床研究。这包括首次证明LH-RH拮抗剂可以抑制男性和女性的LH、FSH以及性类固醇分泌。对墨西哥早期旨在开发新避孕方法的LH-RH拮抗剂的各种研究进行了综述。现代LH-RH拮抗剂西曲瑞克在男性和女性中均显示有效,且可用于治疗子宫平滑肌瘤和良性前列腺增生。还对前列腺癌男性患者使用激动剂D-色氨酸6-LH-RH和拮抗剂西曲瑞克进行了主要的肿瘤学研究,结果证明这两种类似物均具有治疗效果。文中还引用了一些早期生长抑素类似物的内分泌研究,并对生长抑素类似物伐普肽在复发性前列腺癌患者中的一项临床试验进行了综述。所有这些研究在将下丘脑释放激素类似物引入临床医学方面都发挥了重要作用。