Silencing the expression of mitochondrial acyl-CoA thioesterase I inhibits hormone induced sterooidogenesis

CASTILLA ROCÍO; MALOBERTI PAULA; CASTILLO ANA FERNANADA; DUARTE ALEJANDRA; CORNEJO MACIEL, FABIANA; PAZ CRISTINA; PODESTA, ERNESTO J

Congreso; XL Meeting of the Argentine Society for Biochemistry and Molecular Biology Reasearch. (SAIB); 2004

Arachidonic acid (AA) plays a fundamental role in the hormonal regulation of steroidogenesis. We have proposed the involvement of mitochondrial acyl-CoA thioesterase I (MTE-I) as important regulators of AA release in the mechanism of action of trophic hormones. Knocking down the expression levels of MTE-I by antisense or small interfering RNA (siRNA) produced a marked reduction in steroid output of cAMP-stimulated Leydig and adrenal cells. This effect was blunted by a permeable analogue of cholesterol that bypasses the rate-limiting step in steroidogenesis, the transport of cholesterol through the inner mitochondrial membrane. The inhibition of steroidogenesis was overcome by addition of exogenous AA, indicating that the enzymes are part of the mechanism responsible, for AA release involved in steroidogenesis. Knocking down the expression of MTE-I leads to a significant reduction in the expression of Steroidogenic Acute Regulatory protein (StAR), a protein that is induced by AA and that controls the rate-limiting step. Overexpression of MTE-I resulted in an increase of cAMP-induced steroidogenesis. In summary, our results demonstrate a critical role of MTE-I in the hormonal regulation of steroidogenesis as a new pathway of AA release.