Steroidogenic acute regulatory protein: An update on its regulation and mechanism of action

被引:111
作者
Christenson, LK [1 ]
Strauss, JF [1 ]
机构
[1] Univ Penn, Med Ctr, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA
关键词
cholesterol; mitochondria; steroidogenesis; steroidogenic acute regulatory protein; transcription;
D O I
10.1016/S0188-4409(01)00338-1
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Steroidogenic acute regulatory (StAR) protein controls the rate-limiting step in steroidogenesis: the transport of cholesterol from the outer to the inner mitochondrial membrane. Early studies indicated that rate of transcription of the StAR gene is a primary determinant of steroidogenesis. The transcription factors that govern basal and cAMP-dependent StAR expression are reviewed, as are new findings regarding chromatin modifications associated with activation of the StAR promoter. Molecular genetic studies of congenital lipoid adrenal hyperplasia, a rare disease caused by mutations in the StAR gene, and structure-function studies defined two major domains within the StAR protein, the N-terminal mitochondrial targeting sequence and the C-terminal StAR-related lipid transfer (START) domain, which promotes the translocation of cholesterol between the two mitochondrial membranes. Several models of StAR's mechanism of action have been proposed based on a combination of structure/function studies or on the crystal structure of a related START domain. The models-intermembrane shuttle hypothesis, and cholesterol desorption hypothesis-are discussed with respect to the known biochemical and biophysical events associated with steroidogenesis and the structure of StAR. (C) 2001 IMSS. Published by Elsevier Science Inc.
引用
收藏
页码:576 / 586
页数:11
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