Steroidogenic acute regulatory (StAR) protein: what's new?

In response to trophic hormone stimulation of steroidogenic adrenal and gonadal cells, the acute biosynthesis of steroid hormones occurs in the order of minutes to tens of minutes and can be contrasted to chronic regulation, which occurs on the order of hours. The steroidogenic acute regulatory (StAR) protein is an indispensable component in the acute regulatory phase and functions by rapidly mediating the transfer of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where it is cleaved to pregnenolone, the first steroid formed. This transfer of cholesterol constitutes the rate-limiting step in steroidogenesis. To underscore its importance, mutations in the StAR gene have been shown to be the only cause of the potentially fatal disease lipoid congenital adrenal hyperplasia, in which affected individuals synthesize virtually no steroids. Since the cloning of the murine cDNA in 1994, many observations have substantiated the critical role of StAR in regulated steroidogenesis. The purpose of this review will be to summarize briefly some background material on StAR and then attempt to update several recent and interesting findings on the StAR protein.