UNTERSUCHUNGEN ZUR BIOLOGISCHEN AKTIVITÄT DER OESTRIOL-EPIMEREN 16-EPIOESTRIOL, 17-EPIOESTRIOL UND 16,17-EPIOESTRIOL

Abstract

ABSTRACT 16-epioestriol, 17-epioestriol and 16,17-epioestriol are weaker oestrogens than oestriol as determined by the Allen-Doisy test. They are almost as active as oestriol by the intravaginal tetrazolium test and less active in the mouse uterine test. The three epimeres are »impeded oestrogenes«. The dose-effect regression line is flat over a wide range. The three metabolites, when injected together with oestradiol. competetively suppress the growth of the uterus in the rodent, stimulated by oestradiol. Moreover, when assayed on the accessory sex organs of male rats and on the comb of male chickens, they show a marked antiandrogenic action. In this respect 17-epioestriol is the most potent compound. The oestrogenic hyperaemia inducing activity of 16-epioestriol, as measured by the inhibition of the ergotamine induced necrosis of the rat tail, is similar to the activity of oestrone and oestradiol, but greater than that of oestriol. The other triols are less potent in this respect. The activity of the compounds was further tested in the vaginal opening test and the nipple test. For the first time the biological actions of 16-epioestriol and 17-epioestriol have been investigated in the human subject. Both compounds cause proliferation of the vaginal epithelium and a fern like pattern in the cervical mucus. Climacteric symptoms were favourably affected by 16-epioestriol. The three compounds are, however, without any effect on the uterine endometrium and on the excretion of hypophyseal gonadotrophin. In these respects they are similar to oestriol. Physiologically they may be of significance in a peripheral feed back mechanism acting against the primary hormones, between C-16 ketones and ketoles, in balanced reactions and as antagonists of C-16 hydroxylated androgens.