Relation Between Estrogen Inhibitory Activity and Binding to Cytosol of Rabbit and Human Uterus

Abstract

The ability of a group of nonsteroidal antiestrogens to compete with tritiated 17β-estradiol (E2) for binding sites in the cytoplasm of rabbit and human uterus was tested in vitro.The mean relative activities (RA) and ratios of equilibrium constants of association (RAC) compa ed to E2 were much higher for the 2 stilbene derivatives, erythro-MEA and dimethylstilbestrol, than for CN-55-945-27, cisclomiphene, trans-clomiphene, U-11-555A and MER-25. In both species, cis clomiphene was much more active than trans-clomiphene. The RAC's of the non-stilbene derivatives resembled their estrogenic potencies, as found in the literature. Reports of antiestrogenic potencies were extremely variable but were frequently as low as or lower than the RAC. The datasuggest that all these inhibitors are weak estrogens competing effectively for uterine receptors when in high concentration, but rapidly lost from the target organ as a result of their low association constants for the specific binding site. (Endocrinology 87: 1119...