Estrogenic and anti-estrogenic activity of 4-mercuri-17α-estradiol

Abstract

17α-estradiol is a poor estrogen which does compete with 17β-estradiol for the rat uterine cytosol receptor binding site. Presuming that we might effect prolonged retention of 17α-estradiol at this site through use of the affinity labeling approach, we have synthesized 4-mercuri-17α-estradiol (4MEα) for evaluation as both an estrogen and an antiestrogen on direct intrauterine application. The mercury group allows the steroid to form a mercaptide (pseudocovalent) bond with a protein which contains a sulfhydryl group at or near the steroid binding site. 4MEα was a poor estrogen as compared to 4-mercuri-17β-estradiol. As an antiestrogen, 4MEα was equivalent to equimolar amounts of 17α-estradiol when applied two hours before 17β-estradiol in suppressing the induction of glucose-6-phosphate dehydrogenase by the latter. When 4MEα and 17α-estradiol were applied 24 and 48 hours before 17β-estradiol, a persistent antiestrogenic activity was seen with 4MEα, but not with 17α-estradiol. These observations provide evidence that 4MEα is retained at the binding site. Under these conditions, it displays only minimal estrogenicity, but considerable antiestrogenicity by the exclusion of 17β-estradiol from that site.