THE ESTROGENIC PROPERTIESIN VITROOF DIETHYLSTILBESTROL AND SUBSTANCES RELATED TO ESTRADIOL1

Abstract

A number of natural and synthetic estrogens and their structural analogs were tested for their effectiveness in stimulating or inhibiting the estrogen dependent pyridine nucleotide transhydrogenase of human placenta. Dicthylstilbestrol is a potent stimulator of the enzyme system at low concentrations but is an inhibitor at concentrations above 3×10^-6 M. The stilbestrol analog, 1,3 di-p-hydroxylphenyl propane, has only inhibitory effects on the system. Estrololactone, testololactone and A-l testololactone neither stimulate nor inhibit the transhydrogenase. Estrone sulfatc has stimulatory activity equal to estrone or estradiol whereas estradiol disulfate is inactive. It becomes active when the sulfatcs are removed by solvolysis. The thiol analogs of estradiol, with an –SH group in place of the –OH at carbon 17 are not dehydrogenated by cstradiol-17β dehydrogenase nor can they stimulate transhydrogenase. They are potent inhibitors of estradiol-17β dehydrogenase, with the (3 thiol analog being more effective than the a thiol analog, but are only weak inhibitors of the transhydrogenase. Certain inferences are made regarding the structural requirements for activity in stimulating the transhydrogenase system.