Effects of heme oxygenase isozymes on Leydig cells steroidogenesis.

PIOTRKOWSKI, B; PAGOTTO, RM; RECHE, CG; MONZON, CM; BESIO, M; CYMERYNG, CB; PIGNATARO, OP

JOURNAL OF ENDOCRINOLOGY

Año: 2009

0022-0795

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 knownHO-inducer, hemin, increased HO-1 and HO-2 protein levels and HO specific activity. Induction ofHO by hemin inhibited basal, hCG- and dibutyril cAMP (db-cAMP)-induced steroidogenesis in areversible way. When we studied the effect of HO isozymes along the steroid synthesis, we foundthat steroidogenic acute regulatory (StAR) protein levels were decreased and the conversion ofcholesterol to pregnenolone was inhibited by hemin treatment, with no changes in the content ofcholesterol side-chain cleavage enzyme (P450scc). hCG and db-cAMP also stimulated theexpression of HO-1 and HO-2, and HO enzymatic activity in MA-10 cells. Basal and hCGstimulatedtestosterone 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 carbonmonoxide), inhibits cholesterol transport to the inner mitochondrial membrane and Leydig cellsteroidogenesis by binding to the heme group of the cytochrome P450 enzymes, in a similar way aswe described for nitric oxide and ii) the HO isozymes stimulation by LH/hCG would induce anenzymatic system with known antioxidant properties that may be acting as a cytoprotectivemechanism in Leydig cells, as does in adrenal gland.