Recent advances in the role of StAR

Abstract

It has been proposed that the steroidogenic acute regulatory (StAR) protein is the protein responsible for the acute regulation of steroid hormone biosynthesis. Virtually all of the observations made to date are consistent with this proposal. In this short review, background information leading to the discovery and characterization of the StAR protein and several recent and interesting observations concerning this protein are summarized.

Cyclic AMP-induced expression of steroidogenic acute regulatory protein is dependent upon phosphoprotein phosphatase activities

“…In the present study, forskolin stimulated the accumulation of the 30 kDa StAR protein in Y1 cell mitochondria and increased steroid synthesis over time-courses similar to those reported for other steroid-producing cells (Clark et al 1995a,b), in accordance with the StAR protein being required for cholesterol transport and steroid synthesis, suggesting that Y1 cells are similar to primary adrenal tissue and to other steroidogenic cells in this respect (Stocco 1997(Stocco , 1998. The enhanced rate of steroid production by Y1 cells was maintained for up to 20 h, and the increased accumulation of the 30 kDa StAR protein in mitochondria over this time is consistent with the accumulation of a 30 kDA product from a cytosolic active 37 kDa precursor involved in mitochondrial cholesterol transport (see Stocco & Clark 1996, Stocco 1997, 1998.…”

“…Delivery of cholesterol to the inner mitochondrial membrane is the rate-limiting step in steroidogenesis and evidence is accumulating that mitochondrial cholesterol transport is dependent on the expression of the steroidogenic acute regulatory (StAR) protein (Clark et al 1994, Stocco & Clark 1996, Stocco 1997, 1998. For example, expression is restricted to steroidogenic tissues (Clark et al 1995a) and correlates well with changes in steroid production (Nishikawa et al 1996, Liu & Stocco 1997, Ramnath et al 1997, Stocco 1997), experimental over-expression of StAR protein increases steroid production (Clark et al 1994) and the reduced steroid production in congenital lipoid adrenal hyperplasia has been attributed to mutations in the StAR protein gene (Lin et al 1995).…”

Effects of daidzein on testosterone secretion in cultured immature mouse testis

“…It is well known that testosterone is synthesized from cholesterol. The conversion of cholesterol to testosterone involves series of key steroidogenic proteins, such as StAR protein, cytochrome P450scc, and 3β-HSD [11][12][13]. The ratelimiting step in the synthesis of testosterone is the transfer of cholesterol to pregnenolone via P450scc; StAR mediates this rate-limiting step in steroidogenesis [35].…”

“…In addition, testosterone biosynthesis is involved in a series of biochemical processes and is mediated by several key proteins, such as steroidogenic acute regulatory protein (StAR) [11][12][13], cholesterol side-chain cleavage enzyme (p450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) [11]. However, it is whether daidzein influences testosterone biosynthesis by influencing the expression of these proteins has hitherto remained unknown.…”

The mechanism of atrazine action on steroidogenesis in peripubertal rat Leydig cells

“…Upravo je ovde evidentna uloga StAR proteina (engl. Steroidogenic Acute Regulatory proteine), koji vrši translokaciju holesterola do unutrašnje membrane mitohondrija i CYP11A1 (revijalni rad Stocco, 1998;Stocco, 2001). Holesterol transportovan do mitohondrija konvertuje se do pregnenolona delovanjem enzima CYP11A1.…”