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Molecular Endocrinology 11 (2): 138-147
Copyright © 1997 by The Endocrine Society

Characterization of the Promoter Region of the Mouse Gene Encoding the Steroidogenic Acute Regulatory Protein

Kathleen M. Caron, Yayoi Ikeda, Shiu-Ching Soo, Douglas M. Stocco, Keith L. Parker and Barbara J. Clark

Departments of Medicine and Pharmacology Duke University Medical Center (K.M.C., Y.I., S.-C.S., K.L.P.) Durham, North Carolina 27710
Department of Cell Biology and Biochemistry Texas Tech University Health Science Center (D.M.S.) Lubbock, Texas 79430
Department of Biochemistry University of Louisville School of Medicine (B.J.C.) Louisville, Kentucky 40292

Steroidogenic acute regulatory protein (StAR) delivers cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroid hormone biosynthesis. StAR expression is restricted to steroidogenic cells and is rapidly induced by treatment with trophic hormones or cAMP. We analyzed the 5'-flanking region of the mouse StAR gene to elucidate the mechanisms that regulate its cell-specific and hormone-induced expression. In transient transfection assays, a luciferase reporter gene driven by the StAR 5'-flanking region was preferentially expressed by steroidogenic Y1 adrenocortical and MA-10 Leydig cells in a cAMP-responsive manner. 5'-Deletion and site-directed mutagenesis studies identified a region between -254 and -113 that is essential for full levels of promoter activity. This region contains a binding site for the orphan nuclear receptor steroidogenic factor-1 (SF-1) that, although not required for hormone induction, is critical for basal promoter activity, thus implicating SF-1 in StAR expression. Analyses of knockout mice deficient in SF-1 further supported an important role for SF-1 in StAR gene expression. These studies provide novel insights into the mechanisms that regulate StAR gene expression and extend our understanding of SF-1’s global roles within steroidogenic cells. Molecular Endocrinology 11: 138–147, 1997)




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