[Metabolism, structure and biological activity of sex steroids]

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)