Article

Effects of heme oxygenase isozymes on Leydig cells steroidogenesis

Laboratory of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine-CONICET, Vuelta de Obligado 2490, CP 1428 Buenos Aires, Argentina.
Journal of Endocrinology (Impact Factor: 3.59). 08/2009; 203(1):155-65. DOI: 10.1677/JOE-09-0061
Source: PubMed

ABSTRACT In the present study, we demonstrate the expression of heme oxygenase (HO) isozymes, HO-1 and HO-2 (listed as HMOX1 and HMOX2 in the MGI Database), 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 carbon monoxide) 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 nitric oxide, and 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.

0 Followers
 · 
74 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Histamine (HA) is a neurotransmitter synthesized in most mammalian tissues exclusively by histidine decarboxylase enzyme. Among the plethora of actions mediated by HA, the modulatory effects on steroidogenesis and proliferation in Leydig cells (LC) have been recently described. In order to determine if the effects reported in LC could be extrapolated to all steroidogenic systems, we studied the effect of this amine on proliferation and steroidogenesis of the adrenal cortex, using two adrenocortical cell lines as experimental models, the murine Y1 and the human NCI-H295R cells. Even when steroidogenesis was not modified by HA in adrenocortical cells, the biogenic amine inhibited the proliferation of H295R cells. This action was mediated by the activation of the HRH1 receptor subtype and an increase in the production of inositol phosphates as second messengers, causing a cell cycle arrest in the G2/M phase. These results indicate a new role of HA on human adrenocortical cells proliferation that could contribute to a better understanding of tumor pathology as well as to the development of new therapeutic agents.
    Journal of Endocrinology 01/2014; DOI:10.1530/JOE-13-0433 · 3.59 Impact Factor