Interaction of Estrogens on the Vaginal Smear of Spayed Rats

Abstract

Employing the vaginal smear as an index of effect, combinations of various estrogenic substances were tested for interaction. Studies were concentrated at the approximate 50% response level. In a single experiment ED50 doses of the two estrogens in pure form were administered to two groups of spayed rats and a third group was injected with a mixture of one-half of each ed50; in one experiment three intermediate doses were employed. In all of the studies a given proportion of the ED50 of one compound was replaced by the same proportion of the ED50 of the other without mensurable change in biological response. These data are interpreted as indicating simple additive relationships among the compounds tested. Pairs studied were: estradiol-17ß with estriol; and estrone in combination with estradiol-17ß, estriol, methallenestril (Vallestril) and stilbestrol. The additive relationships described here are of particular interest in view of literature reports that indicate an interference between certain pairs of these compounds when uterine growth rather than vaginal cornification was used as an index of activity. This target organ differentiation suggests that various end points of estrogenic action differ in their responses to varying hormonal balances.

Studies on the Interactions of Oestriol and Progesterone

“…Hisaw et al found that oestriol would inhibit the uterine growth stimulated by either oestrone or oestradiol-17 (3 in castrate adult rats, and Huggins & Jensen extended the study to the effects of oestriol and related agents on oestrone-induced uterine growth of young hypophysectomized rats. Systemically, oestradiol-17p, oestrone and oestriol, tested in pairs, had simple additive relationships when rat-vaginal-smear changes were employed as an index of effect (Claringbold, 1955;Edgren & Calhoun, 1957a), although they were mutually antagonistic by the intravaginal route. It has long been known that progesterone is a potent inhibitor of oestrogen-stimulated responses of various types (Roberts & Szego, 1953 Edgren & Calhoun (1960a).…”

Estradienes and 2-Oxaestradienes. Potent Oral Anabolic-Androgenic Agents

“…Progestational activity of compounds II, III and IV in rabbits by means of the Clauberg assay (7) and relative potencies of 0.1, 0.1 and 100 times progesterone, respectively, were obtained. In the rat vaginal smear assay (8), compounds I, III and IV were inactive, while compound II was weakly estrogenic with a relative potency of 6%.…”