IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Effects of heme oxygenase isozymes on Leydig cells steroidogenesis
Autor/es:
PIOTRKOWSKI BÁRBARA; MONZÓN CASANDRA; PAGOTTO ROMINA; RECHE CECILIA; BESIO MARCOS; CYMERYNG CORA; PIGNATARO OMAR P
Revista:
JOURNAL OF ENDOCRINOLOGY
Editorial:
Society for Endocrinology
Referencias:
Lugar: Bristol-Reino Unido; Año: 2009 vol. 203 p. 155 - 165
ISSN:
0022-0795
Resumen:
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 wellknown
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.
Journal of Endocrinology (2009) 203, 155165(2009) 203, 155165