INVESTIGADORES
CASTILLA LOZANO Maria Del Rocio
artículos
Título:
Silencing the expression of mitochondrial acyl-CoA thioesterase I and acyl-CoA synthetase 4 inhibits hormone-induced steroidogenesis.
Autor/es:
MALOBERTI, PAULA-CASTILLA ROCÍO; CASTILLO, FERNANDA; CORNEJO MACIEL, FABIANA; MENDEZ, CARLOS F.; PAZ, CRISTINA; PODESTÁ, ERNESTO J.
Revista:
The FEBS journal
Editorial:
Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies
Referencias:
Lugar: Inglaterra; Año: 2005 vol. 272 p. 1804 - 1814
ISSN:
1742-464X
Resumen:
Arachidonic acid and its lypoxygenated metabolites play a fundamental role in
the hormonal regulation of steroidogenesis. Reduction in the expression of the
mitochondrial acyl-CoA thioesterase (MTE-I) by antisense or small interfering
RNA (siRNA) and of the arachidonic acid-preferring acyl-CoA synthetase (ACS4) by
siRNA produced a marked reduction in steroid output of cAMP-stimulated Leydig
cells. This effect was blunted by a permeable analog of cholesterol that
bypasses the rate-limiting step in steroidogenesis, the transport of cholesterol
from the outer to the inner mitochondrial membrane. The inhibition of
steroidogenesis was overcome by addition of exogenous arachidonic acid,
indicating that the enzymes are part of the mechanism responsible for
arachidonic acid release involved in steroidogenesis. Knocking down the
expression of MTE-I leads to a significant reduction in the expression of
steroidogenic acute regulatory protein. This protein is induced by arachidonic
acid and controls the rate-limiting step. Overexpression of MTE-I resulted in an
increase in cAMP-induced steroidogenesis. In summary, our results demonstrate a
critical role for ACS4 and MTE-I in the hormonal regulation of steroidogenesis
as a new pathway of arachidonic acid release different from the classical
phospholipase A2 cascade.