StAR protein and steroidogenesis are regulated by heme oxygenase isozymes in Leydig cells

MONZÓN CASANDRA; PIOTRKOWSKI BÁRBARA; RECHE CECILIA; BESIO MARCOS; CYMERYNG CORA; PIGNATARO OMAR P

Tucumán, Argentina.

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The aim of this study was to analyze the expression levels of both heme oxygenase (HO) isozymes and the influence of HO activity on steroid production in Leydig cells. We described the expression profile of HO-1 and HO-2 in MA-10 cells. hCG, db-cAMP, and hemin (HO inducer) treatment stimulated the expression of HO-1 and HO-2, and HO enzymatic activity. Hemin also inhibited hCG and db-cAMP- stimulated progesterone synthesis in MA-10 and testosterone in rat Leydig cells. We studied the effect of HO along the steroid synthesis, and found that StAR protein levels were decreased and the conversion of cholesterol to pregnenolone was inhibited by hemin, with no changes in the content of P450scc. We carried out a time course study of hemin action on hCG-stimulated StAR protein and mRNA. While StAR expression was markedly decreased, mRNA was significantly increased, suggesting that HO induction could regulate StAR by modifying its mRNA and protein levels. This results suggest that one of HO products (presumably CO) inhibits cholesterol transport to the inner mitochondrial membrane and steroidogenesis, possibly by binding to the heme group of the cytP450 enzymes;LH/hCG induces an enzymatic system with known antioxidant properties in LC contributing to a fine regulation of male reproductive function.CMM & BP must be considered with the same merit.CONICET PIP5525,UBA X814 & PICT 05-38281 to OPP