Stoichiometric Inhibition of Various 3β-Hydroxysteroid Dehydrogenases by a Substrate Analogue

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Abstract
A synthetic steroid (2[alpha]-cyano-4, 4, 17[alpha]-trimethyl-androst-5-en- 17[beta]-o1-3-one) behaves as a stoichio-metric inhibitor of 3[beta]-hydroxysteroid dehydrogenase in a purified extract of testosterone-induced Pseudomonas testosteroni and in homogenates of bovine and rat adrenal tissues. This inhibitor titrates the activity of the bacterial 3(17-) [beta]-hydroxysteroid dehydrogenase with three 3[beta]- and two 17[beta]-hydroxysteroidal substrates, and that of the mammalian 3[beta]-hydroxysteroid dehydrogenases with the 3[beta]-hy-droxysteroidal substrates. Human adrenal tissue, hyperplastic due to a selectively deficient activity of 3[beta]-hydroxysteroid dehydrogenase, does not bind the inhibitor, while suitable control tissue does. The inhibitor-binding capacity of the purified bacterial preparation is of the same order of magnitude as the amount of inhibitor required to activate the 3[beta]-hydroxysteroid dehydrogenase in this preparation. These results suggest that the prolonged effects of this steroidalcyano ketone in vivo result, at least in part, from its extraordinarily tight binding very near to the active center of 3[beta]-hydroxysteroid dehy-drogenase.

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