Okada H
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Japan.
Nihon Naibunpi Gakkai Zasshi. 1993 Feb 20;69(2):67-79. doi: 10.1507/endocrine1927.69.2_67.
Recently, the action of steroid hormones are interpreted as the results from the interaction with its proper receptors. However, every steroid hormones and steroid drugs have many biological effects, and if one steroid receptor is enough to result in these multiple effects or not is not well known. On the other hand, our experimental results showed that some steroid drugs are metabolized, in vivo, to form several biologically active compounds. Norethindrone, a representative progestational compound, has also some estrogenic and androgenic effects. It was demonstrated, in our laboratory, that the compound was converted, in vivo, to several androgens and to estrogen, ethynyl estradiol. Since it was demonstrated later that ethynyl estradiol but not norethindrone showed estrogenic activity in vitro, it can be concluded that the estrogenic activity of norethindrone was derived from the metabolite of norethindrone, ethynyl estradiol. Although the chemical structure of norethindrone is far different from that of progesterone, it was demonstrated that the progestational effect of norethindrone was derived from the interaction of norethindrone with progesterone receptor. The binding site of norethindrone with the receptor is identical with that of progesterone. Some steroid drugs, such as lynestrenol are inactive, per se, and the conversion of the compound into norethindrone in liver tissue well explained the progestational activity of the compound. In such cases, the studies on the interaction of original compound with receptor in target tissues will give us poor information on the mechanism of steroid action. Some progestational compounds such as medroxyprogesterone acetate has anticancer effect, but norethindrone and the related compounds have no such an effect. This indicates that the receptor for anticancer effect is different from the receptor for common progestational effect. This was confirmed by many ways and the receptor for anticancer effect was partially characterized. Although dydrogesterone is a potent progestational agent and the endometrial response to this compound is almost identical with that to progesterone, it results in neither the elevation of basal body temperature nor an inhibition of ovulation, which are commonly observed with other progestogens. This also raises a doubt on the identity of progesterone receptors in peripheral and central tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
最近，甾体激素的作用被解释为与其特定受体相互作用的结果。然而，每种甾体激素和甾体药物都有许多生物学效应，而一种甾体受体是否足以产生这些多种效应尚不清楚。另一方面，我们的实验结果表明，一些甾体药物在体内会代谢形成几种生物活性化合物。炔诺酮是一种典型的孕激素化合物，也具有一些雌激素和雄激素效应。在我们实验室已证明，该化合物在体内会转化为几种雄激素和雌激素——乙炔雌二醇。由于后来证明乙炔雌二醇而非炔诺酮在体外表现出雌激素活性，所以可以得出结论，炔诺酮的雌激素活性源自其代谢产物乙炔雌二醇。尽管炔诺酮的化学结构与孕酮相差甚远，但已证明炔诺酮的孕激素作用源自炔诺酮与孕酮受体的相互作用。炔诺酮与受体的结合位点与孕酮相同。一些甾体药物，如炔雌醇本身无活性，该化合物在肝组织中转化为炔诺酮很好地解释了其孕激素活性。在这种情况下，对原始化合物与靶组织中受体相互作用的研究将无法为我们提供关于甾体作用机制的充分信息。一些孕激素化合物，如醋酸甲羟孕酮具有抗癌作用，但炔诺酮及相关化合物则无此作用。这表明抗癌作用的受体与常见孕激素作用的受体不同。这已通过多种方式得到证实，且抗癌作用的受体已部分得到表征。尽管地屈孕酮是一种强效孕激素，子宫内膜对该化合物的反应与对孕酮的反应几乎相同，但它既不会导致基础体温升高，也不会抑制排卵，而其他孕激素通常会出现这些现象。这也对周围组织和中枢组织中孕酮受体的一致性提出了质疑。（摘要截选至400字）
