Effects of heme-oxygenase/carbon monoxide system (HO/CO) on testicular steroidogenesis

PIOTRKOWSKI, B; RECHE, C; PAGOTTO, R; BESIO, M; CYMERYNG, C; PIGNATARO, OP

Mar del Plata, Argentina

Congreso; Reunión Nacional de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2007

EFFECTS OF HEME-OXYGENASE/CARBON MONOXIDE SYSTEM (HO/CO) ON TESTICULAR STEROIDOGENESIS Piotrkowski B1, Reche C , Pagotto R , Besio M , Cymeryng CB , Pignataro OP . E-mail: piotrkowski@dna.uba.ar IBYME-CONICET; Dpto Bioq Humana, Medicina, UBA; Dpto Química Biológica-FCEN-UBA, Argentina. Previous results from our lab, showed that nitric oxide (NO) inhibits steroidogenesis in MA-10 Leydig cells, and it is believed that CO, generated from heme in the reaction catalyzed by heme oxygenase, might have similar  regulatory effects as NO. The aim of this study was to investigate the effects of HO/CO on steroidogenesis (P4 synthesis) and StAR protein expression in MA-10 Leydig cells. Hemin, an HO inducer, lowered basal and dibutiryl-cAMP-stimulated (db-cAMP: 1 mM) P4 levels. SnPPIX, an HO inhibitor, increased basal and hCG-stimulated P4 synthesis (hCG: 1 ng/ml, submaximal concentration). Moreover, SnPPIX reverted hemin effects. The incubation of the cells with the permeable analog of cholesterol, 22R-OH-cholesterol or pregnenolone in the presence of SnPPIX suggested that HO/CO inhibits the P450-scc activity. The steroidogenic acute regulatory protein (StAR) regulates the limiting rate step in steroidogenesis: cholesterol transport to the inner mitochondrial membrane. In agreement with P4 results, hemin inhibited the db-cAMPstimulated StAR protein expression. In summary, CO, generated by HO, inhibited P4 synthesis and diminished StAR protein expression in MA-10 Leydig cells, in a similar way to that observed in the presence of NO. In conclusion, CO and NO might have similar effects on steroidogenesis, involving a regulation of StAR protein expression and P450-scc enzyme activity.