IFISE   05411
INSTITUTO DE FISIOLOGIA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Localization and functional activity of cytochrome P450 side chain cleavage enzime (CYP11A1) in the adult rat kidney.
Autor/es:
PAGOTTO MA; ROLDÁN ML; PAGOTTO RM; LUGANO MC; PISANI GB; ROGIC G; MOLINAS SM; TRUMPER SL; PIGNATARO OP; MONASTEROLO LA
Revista:
MOLECULAR AND CELLULAR ENDOCRINOLOGY.
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Año: 2011 p. 253 - 260
ISSN:
0303-7207
Resumen:
Cumulative evidence demonstrated effective downstream metabolism of
pregnenolone in renal tissue. The aim of this study was to evaluate the
expression and functional activity of cytochrome P450 side chain
cleavage enzyme (CYP11A1), which converts cholesterol into pregnenolone,
in adult rat kidney. Immunohistochemical labeling for CYP11A1 was
observed in renal cortex and medulla, on structures identified as distal
convoluted tubule and thick ascending limb of Henle's loop,
respectively. Immunoblotting analysis corroborated the renal expression
of the protein in inner mitochondrial membrane fractions. The incubation
of isolated mitochondria with the membrane-permeant cholesterol
analogue 22R-hydroxycholesterol resulted in efficient formation of
pregnenolone, the immediate precursor for the synthesis of all the
steroid hormones. The low progesterone production rate observed in these
experiments suggested a poor activity of 3β-hydroxysteroid
dehydrogenase enzyme in renal mitochondria. The steroidogenic acute
regulatory protein (StAR), involved in the mitochondrial import of
cholesterol, was detected in renal tissue at both mRNA and protein
level. Immunostaining for StAR showed similar distribution to that
observed for CYP11A1. The expression of StAR and CYP11A1 was found to be
higher in medulla than in cortex. This enhanced expression of
steroidogenesis-related proteins correlated with a greater pregnenolone
synthesis rate and higher steroid hormones tissular content measured in
medulla. In conclusion, we have established the expression and
localization of StAR and CYP11A1 protein, the ability of synthesizing
pregnenolone and a region-specific content of sex hormones in the adult
rat kidney. These data clearly show that the kidney is a steroid
hormones synthesizing organ. It is proposed that the existence in the
kidney of complete steroidogenic machinery would respond to a
physiological significance.