Effects of heme oxygenase isozymes on Leydig cells steroidogenesis.

BARBARA PIOTRKOWSKI; CASANDRA M MONZON; ROMINA M PAGOTTO; CECILIA G RECHE; MARCOS BESIO; CORA CYMERYNG; OMAR PIGNATARO

Buenos Aires, Argentina

Workshop; Workshop: Oxidative stress and antioxidants; 2009

In the present study, we demonstrate the expression of heme oxygenase (HO) isozymes, HO-1 and HO-2, in MA-10 Leydig tumor cells and its effect on steroidogenesis. The well-known HO inducer, hemin, increased both HO-1 and HO-2 protein levels and HO-specific activity. Induction of HO by hemin inhibited basal, hCG-, and dibutyryl cAMP (db-cAMP)-induced steroidogenesis in a reversible way. When we studied the effect of HO isozymes along the steroid synthesis, we found that steroidogenic acute regulatory protein levels were decreased, and the conversion of cholesterol to pregnenolone was inhibited by hemin treatment, with no changes in the content of cholesterol side-chain cleavage enzyme (P450scc). hCG and db-cAMP also stimulated the expression of HO-1 and HO-2, and HO enzymatic activity in MA-10 cells. Basal and hCG-stimulated testosterone synthesis was also inhibited by hemin in rat normal Leydig Cells. Taken together, these results suggest that: i) at least one of HO products (presumably CO) inhibits cholesterol transport to the inner mitochondrial membrane and Leydig cell steroidogenesis by binding to the heme group of the cytochrome P450 enzymes, in a similar way as we described for NO; ii) hCG stimulation results in the induction of an antioxidant enzymatic system (HO) acting as a cytoprotective mechanism in Leydig Cells, as already demonstrated in the adrenal gland. BP and CMM contributed equally to this work.CONICET PIP5525, UBA X814, PICT 05-38281 to OPP.