Fatty acids as stimulatiors of cholesterol transport and metabolism in adrenal and leydig cells

CASTILLO, FERNANDA; CORNEJO MACIEL, FABIANA; CASTILLA, ROCÍO; MALOBERTI, PAULA; DUARTE, ALEJANDRA; TOLEDO, FERNANDA; MEULI, FLAVIA; PAZ, CRISTINA; PODESTÁ, ERNESTO J.

Boston, Massachussets, Estados Unidos

Congreso; XIIAdrenal Cortex and V th Molecular Steroidogenesis Conference; 2006

The Endocrine Society Adrenal

 Previously we showed a new mechanism that controls the levels of free AA. This hormone regulated mechanism involves the concerted action of two enzymes, an acyl-CoA synthetase and an acyl-CoA thioesterase. The synthetase, named ACS4, was described as an AA preferring enzyme that is preferentially expressed in steroidogenic tissuees. The thioesterase es a member of a family with long chain fatty acyl-CoA thioesterase activity which is associated with the inner mitochondrial membrane, named Acot2. The steroidogenic hormones regulate both enzymes: while Acot2 is activated by phosphorylation and substrate availability, ACS4 is rapidly induced after hormone treatment. The participation of ACS4 and Acot2 as obligatory component of AA release, StAR induction and steroidogenesis was confirmed by recent experiments showing that steroid production is inhibited in Y1 and MA-10 cells by silencing the expression of both Acot2 and ACS4.These results led us to propouse that ACS4 acts by sequestering free AA forming and intracellular pool of AA-CoA that is delivered to Acot2 which will, in turn, release AA in a specific compartment of the cell (the mitochondria). In the present report we demonstrate that in the acute phase (early response) of sterod synthesis, the realease of AA into the mitochondria is stimulated by cAMP and it is able to increase cholesterol transport