Multiple contributions from long-chain fatty acid metabolism in Y-1 and MA-10 cells

Acute steroidogenesis in either Y-1 or MA-10 cells is sensitive to different effects of fatty acids compare to a chronic stimulation. A 3-h stimulation of StAR expression in both cell types was completely blocked by NDGA and AA861, each functioning as lipoxygenase inhibitors. However, the acute 15-min stimulation in Y-1 cells was inhibited by these agents by distinct mechanisms. The inhibition by NDGA was reversed by arachidonic, linoleic, and oleic acids. The inhibition by AA861 was insensitive to reversal by these acids. StAR expression was not affected by these short-term inhibitor treatments. These more rapid fatty acid reversible effects of NDGA are consistent with previously reported inhibition of mitochondrial Acyl CoA ligase. This may function in cooperation with StAR and PBR in providing fatty acid regulation of mitochondrial cholesterol transport. The acute effect of AA861 supports the involvement of an NDGA-insensitive lipoxygenase in the acute stimulation of mitochondrial cholesterol metabolism. The activity of MA-10 cells during prolonged treatments with cAMP appears to utilize each of these processes, which depend on different metabolism of fatty acids.