Post-coital contraceptive activity and estrogen receptor binding affinity of phenolic steroids

Abstract

Estradiol, estradiol-16a, estriol and a series of positional isomers of estriol were tested for their post-coital contraceptive activity, and their ability to compete with estradiol for the cytosolic estrogen receptor protein of rat uteri. Estrogenicity was determined for each compound in immature rats with single injections and in mature castrated rats by injecting the lowest fully contraceptive dose for four consecutive days. All compounds were active anti-implantational agents, varying in required dosage from 4 μg to 2000 μg (total dosage over 4 days). The rank order of contraceptive activity was found to be: estradiol ≫ estriol = epiestriol > 11β - (OH) - estradiol > estradiol - 16α > 7α-(OH)-estradiol ≫ 6β-(OH)-estradiol, while the order of estrogenicity at levels of contraceptive activity in the ovariectomized mature rat was: epiestriol = estriol < 7α - (OH) - estradiol < estradiol - 16α < 6β - (OH) - estradiol = 11β - (OH) - estradiol ≪ estradiol-17β. Reasonably good correlation between competition for estrogen receptor and anti-implantational activity was observed. The most active binding competitors were estradiol-16a, epiestriol, and estriol which showed an affinity from 50-20% that of estradiol, while the other compounds had 3% or less binding competition for estradiol. © 1977 by The Endocrine Society.