Asch R H, Smith C G, Siler-Khodr T M, Bartke A
Obstet Gynecol. 1982 Mar;59(3):303-8.
The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 micrograms/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P less than .01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 micrograms/ml azastene in the incubation media (P less than .05 and less than .01, respectively). The availability of a compound that blocks in vivo and in vitro gonadal steroidogenesis opens a new approach to postcoital contraception in primates because of its luteolytic and interceptive activity. The possible mechanisms of action of azastene are discussed.
在3种不同模型中研究了4,4,17-α-三甲基雄甾-5-烯-[2,3,-d]异恶唑-17-醇（氮杂烯）阻断类固醇生成的能力。在恒河猴黄体期的不同日子口服500毫克该药物，可导致循环孕酮浓度显著降低，在某些情况下还会使月经提前来潮。在黄体中期同时给予人绒毛膜促性腺激素（hCG）并不能克服氮杂烯的黄体溶解作用。浓度为50微克/毫升的氮杂烯可抑制去包膜小鼠睾丸对hCG刺激的睾酮分泌[对照组，1165±196纳克/毫升，氮杂烯组，306±40纳克/毫升（P<0.01）]。在孵育培养基中存在25和50微克/毫升氮杂烯时，恒河猴黄体分散的黄体细胞孕酮生成受到显著抑制（分别为P<0.05和P<0.01）。由于其黄体溶解和阻断作用，一种能在体内和体外阻断性腺类固醇生成的化合物为灵长类动物的性交后避孕开辟了新途径。本文讨论了氮杂烯可能的作用机制。
