This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burgos-Trinidad, M. Articles by Payne, A. H. Search for Related Content PubMed PubMed Citation Articles by Burgos-Trinidad, M. Articles by Payne, A. H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB TESTOSTERONE

Repression of cAMP-Induced Expression of The Mouse P450 17-Hydroxylase/C17-20 Lyase Gene (Cyp17) by Androgens

Department of Obstetrics and Gynecology (M.B.-T., G.L.Y., M.R.M., A.H.P.) and The Reproductive Sciences Program (M.B.-T., D.M.R., A.H.P.) Department of Human Genetics (A.S., D.M.R.) Department of Biological Chemistry (G.L.Y., A.H.P.) The University of Michigan Ann Arbor, Michigan 48109

In primary cultures of mouse Leydig cells, testosterone represses the cAMP-induced de novo synthesis of P450 17-hydroxylase/C17-20 lyase (P450c17) protein and the accumulation of P450c17 mRNA, via an androgen receptor (AR)-mediated mechanism. To examine the mechanism by which androgens repress the cAMP-induced expression of the mouse Cyp17 gene, constructs containing 5'-flanking sequences of the mouse Cyp17 linked to the chloramphenicol acetyltransferase (CAT) reporter gene were cotransfected into MA-10 tumor Leydig cells with a mouse AR expression plasmid. In the presence of dihydrotestosterone, the cAMP-induced expression of a reporter construct containing -1021 bp of Cyp17 promoter sequences was repressed. In contrast, no repression by dihydrotestosterone was observed when the -1021 bp Cyp17-CAT construct was cotransfected with a human AR expression plasmid missing the second zinc finger of the DNA-binding domain, indicating that DNA binding is involved in AR-mediated repression of Cyp17 expression. Analysis of deletions of the -1021 bp fragment demonstrated that -346 bp of 5'-flanking region of the mouse Cyp17 promoter are sufficient to confer androgen repression of the cAMP-induced expression of Cyp17. Deoxyribonuclease I footprinting analysis indicated that the AR interacts with sequences between -330 and -278 bp of the Cyp17 promoter. This region overlaps with the previously identified cAMP-responsive region located between -346 and -245 bp of the Cyp17 promoter. These results suggest that AR-mediated repression involves binding of the AR to sequences in the cAMP-responsive region of the Cyp17 promoter, possibly interfering with the binding of the protein(s) that mediate cAMP induction of Cyp17.

This article has been cited by other articles:

				S. M. Eacker, N. Agrawal, K. Qian, H. L. Dichek, E.-Y. Gong, K. Lee, and R. E. Braun Hormonal Regulation of Testicular Steroid and Cholesterol Homeostasis Mol. Endocrinol., March 1, 2008; 22(3): 623 - 635. [Abstract] [Full Text] [PDF]

				S. M. Eacker, J. E. Shima, C. M. Connolly, M. Sharma, R. W. Holdcraft, M. D. Griswold, and R. E. Braun Transcriptional Profiling of Androgen Receptor (AR) Mutants Suggests Instructive and Permissive Roles of AR Signaling in Germ Cell Development Mol. Endocrinol., April 1, 2007; 21(4): 895 - 907. [Abstract] [Full Text] [PDF]

				M. G. Yeo, Y.-G. Yoo, H.-S. Choi, Y. K. Pak, and M.-O. Lee Negative Cross-Talk between Nur77 and Small Heterodimer Partner and Its Role in Apoptotic Cell Death of Hepatoma Cells Mol. Endocrinol., April 1, 2005; 19(4): 950 - 963. [Abstract] [Full Text] [PDF]

				Q. Zhou, J. E. Shima, R. Nie, P. J. Friel, and M. D. Griswold Androgen-Regulated Transcripts in the Neonatal Mouse Testis as Determined Through Microarray Analysis Biol Reprod, April 1, 2005; 72(4): 1010 - 1019. [Abstract] [Full Text] [PDF]

				A. M. Braun and P. Thomas Androgens Inhibit Estradiol-17{beta} Synthesis in Atlantic Croaker (Micropogonias undulatus) Ovaries by a Nongenomic Mechanism Initiated at the Cell Surface Biol Reprod, November 1, 2003; 69(5): 1642 - 1650. [Abstract] [Full Text] [PDF]

				N. A. Hanley, W. E. Rainey, D. I. Wilson, S. G. Ball, and K. L. Parker Expression Profiles of SF-1, DAX1, and CYP17 in the Human Fetal Adrenal Gland: Potential Interactions in Gene Regulation Mol. Endocrinol., January 1, 2001; 15(1): 57 - 68. [Abstract] [Full Text]

				A. G. Mensah-Nyagan, J.-L. Do-Rego, D. Beaujean, V. Luu-The, G. Pelletier, and H. Vaudry Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System Pharmacol. Rev., March 1, 1999; 51(1): 63 - 82. [Abstract] [Full Text] [PDF]

				X. Chu, C. J. Corbin, M. A. Kaminski, and A. J. Conley Unique Regulation of CYP17 Expression in the Trophectoderm of the Preattachment Porcine Blastocyst Endocrinology, February 1, 1999; 140(2): 632 - 640. [Abstract] [Full Text]