Krey L C, Robbins R, McEwen B S
Fertil Steril. 1981 Apr;35(4):467-72. doi: 10.1016/s0015-0282(16)45446-4.
We investigated the relationship between intracellular androgen and estrogen receptors within the brain-pituitary complex and danazol suppression of luteinizing hormone secretion in castrated rats. Danazol did not influence 3H-estradiol-estrogen receptor interactions within the brain and pituitary but did suppress 3H-dihydrotestosterone-androgen receptor interactions within this neuroendocrine complex. To study the significance of these danazol-androgen receptor interactions, the drug was administered to androgen receptor-deficient pseudohermaphrodite or flutamide-treated male rats. In both instances, danazol suppression of luteinizing hormone release was markedly attenuated or absent. These findings point to danazol-androgen receptor interactions within the brain-pituitary complex as a key step in this drug's antigonadotropic actions. Whether the active drug form is danazol itself or a metabolite is subject to further study.
我们研究了脑垂体复合体中细胞内雄激素受体和雌激素受体之间的关系，以及达那唑对去势大鼠促黄体生成素分泌的抑制作用。达那唑不影响脑和垂体中³H-雌二醇与雌激素受体的相互作用，但确实抑制了该神经内分泌复合体中³H-双氢睾酮与雄激素受体的相互作用。为了研究这些达那唑与雄激素受体相互作用的意义，将该药物给予雄激素受体缺陷的假两性畸形大鼠或氟他胺处理的雄性大鼠。在这两种情况下，达那唑对促黄体生成素释放的抑制作用均明显减弱或消失。这些发现表明，脑垂体复合体中达那唑与雄激素受体的相互作用是该药物抗促性腺作用的关键步骤。活性药物形式是达那唑本身还是其代谢产物有待进一步研究。
