竞争性孕酮拮抗剂：睾酮和19-去甲睾酮衍生物的受体结合及生物活性

Competitive progesterone antagonists: receptor binding and biologic activity of testosterone and 19-nortestosterone derivatives.

作者信息

Reel J R, Humphrey R R, Shih Y H, Windsor B L, Sakowski R, Creger P L, Edgren R A

出版信息

Fertil Steril. 1979 May;31(5):552-61. doi: 10.1016/s0015-0282(16)44003-3.

Abstract

Testosterone and 19-nortestosterone derivatives were evaluated in a developmental scheme designed to identify competitive progesterone antagonists having abortifacient activity. Compounds that displayed significant binding to the rabbit uterine progesterone receptor were followed in biologic tests for progestational, antiprogestational, and abortifacient activities. Of the seven compounds tested for both progestational and antiprogestational activity, only one, 5 alpha-dihydronorethindrone, behaved exclusively as an antagonist. Five other 19-nortestosterones (19-nortestosterone, 17 beta-hydroxyestra-4, 9(10)-dien-3-one, norethindrone, norethindrone acetate, and R 2323) proved to be mixed agonists/antagonists. 5 alpha-Dihydronorethindrone, norethindrone, and 19-nortestosterone terminated pregnancy during the postnidatory period in rats; in addition, the latter two compounds inhibited progesterone-supported pregnancy in spayed rats and curtailed pregnancy during the postnidatory period in hamsters. These results demonstrate that several 19-nortestosterone derivatives bind to the uterine progesterone receptor and behave either as antagonists or mixed agonists/antagonists.

摘要

在一项旨在鉴定具有堕胎活性的竞争性孕酮拮抗剂的发育方案中，对睾酮和19-去甲睾酮衍生物进行了评估。对那些与兔子宫孕酮受体显示出显著结合的化合物进行了孕激素、抗孕激素和堕胎活性的生物学测试。在接受孕激素和抗孕激素活性测试的7种化合物中，只有一种，即5α-二氢炔诺酮，仅表现为拮抗剂。其他5种19-去甲睾酮（19-去甲睾酮、17β-羟基雌-4,9(10)-二烯-3-酮、炔诺酮、炔诺酮醋酸酯和R 2323）被证明是混合激动剂/拮抗剂。5α-二氢炔诺酮、炔诺酮和19-去甲睾酮在大鼠着床后终止妊娠；此外，后两种化合物在去卵巢大鼠中抑制了孕酮支持的妊娠，并在仓鼠着床后缩短了妊娠。这些结果表明，几种19-去甲睾酮衍生物与子宫孕酮受体结合，并表现为拮抗剂或混合激动剂/拮抗剂。