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Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292
Address all correspondence and requests for reprints to: Dr. Barbara J. Clark, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40292. E-mail: bjclark{at}louisville.edu
De novo synthesis of the steroidogenic acute regulatory protein (StAR) in response to trophic hormonal stimulation of steroidogenic cells is required for the delivery of cholesterol from the mitochondrial outer membrane to the mitochondrial inner membrane and the cytochrome P450 side-chain cleavage enzyme. StAR expression is transcriptionally regulated by cAMP-mediated mechanisms, and we have identified a 45-bp region within the mouse promoter that is important for cAMP responsiveness of the gene. This region, located between -105 and -60 of the start site of transcription, contains a SF-1-binding site, a highly conserved C/EBPß -AP-1-nuclear receptor half-site sequences (CAN region), and a GATA-4-binding site. The SF-1 element and CAN region are required for full basal activity, whereas the GATA-4 element may account for 20% of the cAMP response in MA-10 mouse Leydig tumor cells. A cAMP-dependent protein-DNA complex was observed with the CAN region and mutation of a nonconsensus AP-1 site within this region greatly diminished promoter strength. Complex protein-DNA interactions within the cAMP response region (-105/-60) were shown to require the SF-1 element (-95), suggesting that SF-1 is required for protein-DNA interaction at the CAN (-79) region and maximal activity of the promoter.
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Y. Wang, D. C. Newton, T. L. Miller, A.-M. Teichert, M. J. Phillips, M. S. Davidoff, and P. A. Marsden An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells Am. J. Pathol., January 1, 2002; 160(1): 369 - 380. [Abstract] [Full Text] [PDF]
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W. K. Shea-Eaton, M. J. Trinidad, D. Lopez, A. Nackley, and M. P. McLean Sterol Regulatory Element Binding Protein-1a Regulation of the Steroidogenic Acute Regulatory Protein Gene Endocrinology, April 1, 2001; 142(4): 1525 - 1533. [Abstract] [Full Text]
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D. B. Hales Editorial: Gonadal-Specific Transcription Factors--GATA (Go) 4 It! Endocrinology, March 1, 2001; 142(3): 974 - 976. [Full Text] [PDF]
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S. L. Gyles, C. J. Burns, B. J. Whitehouse, D. Sugden, P. J. Marsh, S. J. Persaud, and P. M. Jones ERKs Regulate Cyclic AMP-induced Steroid Synthesis through Transcription of the Steroidogenic Acute Regulatory (StAR) Gene J. Biol. Chem., September 7, 2001; 276(37): 34888 - 34895. [Abstract] [Full Text] [PDF]
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