Inhibiton of human placental 17 beta-hydroxysteroid dehydrogenase by steroids and nonsteroidal alcohols: aspects of inhibitor structure and binding specificity

Inhibition of human placental 17β-hydroxysteroid dehydrogenase by C₁₈ and C₁₉ steroids and nonsteroidal alcohols was assayed at pH 9.0 with 17β-estradiol 3-methyl ether and NAD⁺ as reactants. The nonstaroidal alcohols tested were poor inhibitors. Cyclopentanol and cyclohexanol had K_i values greater than 5 mm. Nonaromatic C₁₈ and C₁₉ steroids with oxygen functions at both positions 3 and 17 gave no detectable inhibition or had K_i, values greater than or equal to 160 μm. 3μ-Hydroxy-5,16-androstadiene, 5-androsten-3β-ol, 1,3,5(10)-estratrien-3-ol, and 1,3,5(10),16-estratetraen-3-ol, steroids lacking a C(17) oxygen function, had K_i values of 1.8, 6.0, 0.04, and 0.17 μm, respectively, demonstrating that both C₁₈ and C₁₉ steroids can bind at the steroid site. Binding specificity is narrowed and binding affinity for nonaromatic steroids weakened by oxygen functions at C(17) or both C(3) and C(17). The structural implications of the specificity data for steroid recognition and complex formation and in vivo control of enzyme activity are discussed.