达那唑与类固醇受体的结合及转位

Danazol binding and translocation of steroid receptors.

作者信息

Chamness G C, Asch R H, Pauerstein C J

出版信息

Am J Obstet Gynecol. 1980 Feb 15;136(4):426-9. doi: 10.1016/0002-9378(80)90665-1.

Abstract

Danazol, an isoxazol derivative of ethinyl testosterone which suppresses gonadotropin levels and acts as a weak androgen, is shown by competition studies to bind rat androgen receptor (Ki 10(-8M) and progestin receptor (Ki 10(-7)M) but not estrogen receptor. Effective antigonadotropin doses to the rat in vivo translocate only androgen receptor to target cell nuclei; nuclear receptor levels remain elevated more than 6 hours. The same translocation occurs when rat uteri are incubated with danazol in vitro, showing that the action of danazol is direct and probably does not require metabolic conversion of the drug.

摘要

达那唑是乙炔睾酮的异恶唑衍生物，可抑制促性腺激素水平并作为一种弱雄激素起作用。竞争研究表明，它能与大鼠雄激素受体（Ki 10⁻⁸M）和孕激素受体（Ki 10⁻⁷M）结合，但不与雌激素受体结合。在体内对大鼠使用有效的抗促性腺激素剂量时，仅雄激素受体易位至靶细胞核；核受体水平在6小时以上仍保持升高。当大鼠子宫在体外与达那唑一起孵育时也会发生同样的易位，这表明达那唑的作用是直接的，可能不需要药物的代谢转化。