Expression of the steroidogenic acute regulatory (StAR) protein: A novel LH-induced mitochondrial protein required for the acute regulation of steroidogenesis in mouse leydig tumor cells

Abstract

The acute response of steroidogenic cells to hormone stimulation is the mobilization of cholesterol from cellular stores and the outer mitochondrial membrane to the inner mitochondrial membrane and the cholesterol side-chain cleavage complex (CSCC) where the first enzymatic reaction occurs. It has been well established that the translocation of cholesterol from the outer to the inner mitochondrial membrane requires de novo protein synthesis and that this process is the rate-limiting, regulated step in steroidogenesis. We have purified a novel mitochondrial protein (named StAR) from the MA-10 mouse Leydig tumor cells which we have previously proposed represents a strong candidate for the newly synthesized regulatory protein in steroidogenesis. The cDNA for StAR was cloned and we have demonstrated that expression of the StAR protein in MA-10 cells in the absence of hormone stimulation results in a 3 fold increase in progesterone production compared to mock transfected cells. These studies indicate a direct relationship between StAR expression and steroidogenesis, therefore, we conclude that StAR is required in the acute regulation of steroidogenesis.