SPECIFIC EFFECT OF ARACHIDONIC-ACID ON 17-BETA-HYDROXYSTEROID DEHYDROGENASE IN RAT LEYDIG-CELLS

It is well known that arachidonic acid (AA) acts as an intratesticular factor regulating luteinizing hormone-mediated testicular steroidogen esis, The present studies were conducted to determine the effect of AA on steroidogenic enzymes in rat Leydig cells, Exogenously added AA si gnificantly inhibited 22(R)-hydroxy-cholesterol-stimulated testosteron e production, which is a clear indication that AA is acting at some po int after cholesterol transport to the inner mitochondrial membrane, A A failed to block the conversion of 22(R)-hydroxycholesterol to pregne nolone, indicating that the cytochrome P-450 side-chain cleavage enzym e complex is not the site of inhibition, The present results demonstra te that only 17 beta-hydroxysteroid dehydrogenase seems to be involved in the AA action, since nearly 60% inhibition of testosterone product ion was found when the cells were incubated with androstenedione, Furt hermore, no effect of AA was found, when androstenediol was used as su bstrate in the testosterone synthesis, which indicates that 3 beta-hyd roxysteroid dehydrogenase is not affected by AA. The conversion of AA to its metabolites is not required for its action on 17 beta-hydroxyst eroid dehydrogenase and the activation of protein kinase C is not invo lved in the inhibitory effect. (C) 1998 Federation of European Biochem ical Societies.