3α-hydroxysteroid dehydrogenase activity in rat liver and skin

Abstract

3α-Hydroxysteroid dehydrogenase (3αHSD) is one of the main enzymes involved in the metabolism of the active androgen, dihydrotestosterone (DHT). 3αHSD catalyzes the reversible reduction of DHT to 5α-androstane-3α, 17β-diol (3αDIOL). The equilibrium of 3αHSD reductive and oxidative activity is an important factor in the regulation of intracellular levels of DHT. In this study, we determined the kinetic characteristics of 3αHSD in the subcellular fractions of female rat liver and abdominal skin. The enzyme expressed its activity in the cytosol and microsomal fractions of both of these tissues. It showed higher activity with the phosphorylated cofactors, NADPH and NADP, and was inhibited by indomethacin. The V max values of 3αHSD in the cytosol were 10-fold higher than the V max values in the microsomes in both the liver and skin. In both tissues, the K m values with DHT as the substrate (reductive) were lower than the K m with 3αDIOL as the substrate (oxidative). Although the V max values of the oxidative reaction were higher than the V max values of the reductive reaction in both liver and skin, the low K m values and the higher V max /K m ratio for DHT indicated that the reduction of DHT to 3αDIOL was the favored reaction. The enzyme kinetics of 3αHSD suggest that neither tissue accumulates DHT, but promptly converts it to 3αDIOL. When DHT reduction by 3αHSD in the liver and skin was compared on the basis of total tissue weight, the ability to metabolize DHT to 3αDIOL was 12-fold higher in the liver, suggesting that the liver is more effective in DHT reduction to 3αDIOL. (Steroids 59:259–264, 1994)