Bromocriptine-induced inhibition of hydroxylase/lyase activity of adult rat Leydig cells

Abstract

The present in vitro studies using a suspension of Leydig cells from adult rat testis demonstrated that bromocriptine (BR, 2 × 10-5M) inhibits hCG-stimulated testosterone production (in the presence of submaximal and maximal doses of hCG), while basal production was unaffected. When the cells were exposed to 8-bromo-cAMP either in the presence or absence of hCG, the inhibitory effect of BR was not reversed. In intact cells, BR inhibited conversion of progesterone and 17-hydroxy-progesterone to testosterone while conversion of androstenedione was not affected. Incubation of homogenates of Leydig cells in the presence of limiting NADPH concentrations (≤ 0.1 mM) resulted in significant BR-induced inhibition of conversion of progesterone (10 μM) to testosterone, while in the presence of "high" concentrations of NADPH (≥ 0.5 mM) BR was without effect. Present results suggest that BR inhibits androgen production at the level of the microsomal enzymes 17α-hydroxylase and/or 17,20-lyase. The inhibitory effect of BR using homogenates of Leydig cells was evident only in the presence of limiting NADPH concentrations that suggests a competitive-like pattern of inhibition, but mechanisms by which BR decreases activity of microsomal enzymes remain to be determined. © 1993.