CHARACTERISTICS OF THE NUCLEAR AND MICROSOMAL STEROID Δ4-5α-HYDROGENASE OF THE RAT PROSTATE

Abstract

ABSTRACT Steroid Δ4-5α-hydrogenase was intracellularly localized in the nuclear and microsomal fractions of the rat ventral prostate (Nozu Sc Tamaoki 1973). The nuclear Δ4-5α-hydrogenase was found to have the following enzymatic properties essentially similar to the microsomal Δ4-5α-hydrogenase, with regard to the metabolism of [4-14C] testosterone in the presence of NADPH: The optimum pH of the enzymes in the two fractions was around 7.0 and the maximal conversion rates were obtained at a temperature of 35 to 40°C. The apparent Km values of the nuclear and microsomal Δ4-5α-hydrogenases were estimated respectively as 1.05 and 0.90 μmol/l, while the Km value of the hepatic microsomal Δ4-5α-hydrogenase was simultaneously estimated as 154 μmol/l. Among steroids, the most potent inhibitor group on the enzymatic 5α-hydrogenation of testosterone was Δ 4-3-oxo-C-21 steroids such as progesterone and 17α-hydroxyprogesterone, which were competitively converted into their 5α-hydrogenated metabolites in the highest rates. Among some anti-androgens, cyproterone and its acetate hardly inhibited the activities of the nuclear and microsomal enzymes, whereas etienic acid (4-androsten-3-one-17β-carboxylic acid), oestradiol-17β and diethylstilboestrol markedly inhibited both prostatic enzymes in a competitive manner. The Ki values of etienic acid, oestradiol-17β and diethylstilboestrol for the nuclear Δ4-5α-hydrogenase were respectively 1.50, 0.49 and 1.02 μmol/l, indicating similar affinities of these for the nuclear enzyme to that of testosterone.