Bromocriptine-induced inhibition of hydroxylase/lyase activity of adult rat Leydig cells.
The present in vitro studies using a suspension of Leydig cells from adult rat testis demonstrated that bromocriptine (BR, 2 x 10(-5)M) 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 (< or = 0.1 mM) resulted in significant BR-induced inhibition of conversion of progesterone (10 microM) to testosterone, while in the presence of "high" concentrations of NADPH (> or = 0.5 mM) BR was without effect. Present results suggest that BR inhibits androgen production at the level of the microsomal enzymes 17 alpha-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.
Kovacevic
R
R
Institute of Biology, University of Novi Sad, Serbia.
Sarac
M
M
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D006063:Chorionic Gonadotropin; D065607:Cytochrome P-450 Enzyme Inhibitors; D001971:Bromocriptine; D013739:Testosterone; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases