Receptor binding of STS 557.

Abstract

Binding of the new progestagen STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) to progesterone receptors was investigated by competition experiments using cytosol preparations from chick oviduct, rat uterus, rabbit uterus and human endometrium. A high competitive potency of STS 557 was found in the mammalian systems used. The binding affinity was about 20% that of progesterone. Binding to cytosol receptors of the chick oviduct was two orders lower. Five derivatives of STS 557 were compared with respect to progesterone receptor binding by using rabbit uterus cytosol. The hydrogenated 3-oxo compounds exhibited receptor affinities similar to the parent compound as for as the planarity of the steroid ring system was sustained. 5 beta-H compounds were nearly inactive. Additionally, binding to the androgen receptor of rat prostate cytosol was measured. STS 557 and its planar derivatives were found to be effective competitors for 5 alpha-dihydrotestosterone (DHT) exhibiting binding affinities about one fifth that of DHT. The findings are discussed with respect to the chemical structures and the in vivo effects of STS 557.