help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shea-Eaton, W. K.
Right arrow Articles by McLean, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shea-Eaton, W. K.
Right arrow Articles by McLean, M. P.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Endocrinology Vol. 142, No. 4 1525-1533
Copyright © 2001 by The Endocrine Society

ARTICLES

Sterol Regulatory Element Binding Protein-1a Regulation of the Steroidogenic Acute Regulatory Protein Gene1

Wendy K. Shea-Eaton, Marie Joy Trinidad, Dayami Lopez2, Anna Nackley and Mark P. McLean

Department of Obstetrics and Gynecology and Molecular Biology and Biochemistry University of South Florida, College of Medicine, Tampa, Florida 33606

Address all correspondence and requests for reprints to: Dr. Mark P. McLean, University of South Florida, Department of Obstetrics and Gynecology, 4 Columbia Drive, Suite 529, Tampa, Florida 33606. E-mail: mmclean{at}com1.med.usf.edu

The binding of tropic hormones to their specific receptors in steroidogenic cells stimulates the cAMP second-messenger system in the presence of steroidogenic factor-1 (SF-1) to increase expression of steroidogenic acute regulatory (StAR) protein, facilitating the transfer of cholesterol to the inner mitochondrial membrane. The increased use of cholesterol in steroidogenesis triggers activation of sterol- sensitive genes through a second regulatory pathway involving the binding of sterol regulatory element (SRE)-binding proteins (SREBP) to SREs located in the promoter regions of these genes. A search of the rat StAR promoter revealed five potential SRE sites, which demonstrated specific binding with recombinant SREBP-1a. Overexpression of SREBP-1a, -1c or -2 in HTB-9 cells cotransfected with the rat StAR promoter resulted in an increase in promoter-driven luciferase activity. In addition, SREBP-1a was able to activate the StAR promoter through an E-box but only in a promoter construct lacking SREs. SREBPs are known to be weak transcriptional activators and require the presence of additional coactivators like Sp1 and nuclear factor-Y (NF-Y) to elicit maximum activation. Electrophoretic mobility shift assays demonstrated that Sp1, SF-1, and NF-Y enhanced SREBP-1a binding to SREs in the StAR promoter. There was a 4-fold increase in StAR promoter luciferase reporter gene expression when HTB-9 cells were cotransfected with expression vectors for SREBP-1a and NF-Y. In addition, the combined action of SREBP-1a and SF-1 increased both basal (1.6-fold) and cAMP-induced (3.5-fold) activation of the rat StAR promoter. Although Sp1 enhanced SREBP-1a binding to an SRE, Sp1 was not able to increase StAR promoter activity in the presence of SREBP-1a. These results suggest that SREBP-induced regulation of the rat StAR gene is responsive to selective combinations of transcriptional cofactors that could necessitate the convergence of multiple regulatory pathways to enhance gene transcription.




This article has been cited by other articles:


Home page
 Exp. Biol. Med.Home page
H. A. LaVoie and S. R. King
Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B
Experimental Biology and Medicine, August 1, 2009; 234(8): 880 - 907.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Palaniappan and K.M.J. Menon
Regulation of Sterol Regulatory Element-Binding Transcription Factor 1a by Human Chorionic Gonadotropin and Insulin in Cultured Rat Theca-Interstitial Cells
Biol Reprod, August 1, 2009; 81(2): 284 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
V. Besnard, Y. Xu, and J. A. Whitsett
Sterol response element binding protein and thyroid transcription factor-1 (Nkx2.1) regulate Abca3 gene expression
Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1395 - L1405.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Q. Liu, K. A. Merkler, X. Zhang, and M. P. McLean
Prostaglandin F2{alpha} Suppresses Rat Steroidogenic Acute Regulatory Protein Expression via Induction of Yin Yang 1 Protein and Recruitment of Histone Deacetylase 1 Protein
Endocrinology, November 1, 2007; 148(11): 5209 - 5219.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. H. Mellon, S. R. Bair, C. Depoix, J.-L. Vigne, N. B. Hecht, and P. B. Brake
Translin Coactivates Steroidogenic Factor-1-Stimulated Transcription
Mol. Endocrinol., January 1, 2007; 21(1): 89 - 105.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Ozbay, A. Rowan, A. Leon, P. Patel, and M. B. Sewer
Cyclic Adenosine 5'-Monophosphate-Dependent Sphingosine-1-Phosphate Biosynthesis Induces Human CYP17 Gene Transcription by Activating Cleavage of Sterol Regulatory Element Binding Protein 1
Endocrinology, March 1, 2006; 147(3): 1427 - 1437.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. F. Clem and B. J. Clark
Association of the mSin3A-Histone Deacetylase 1/2 Corepressor Complex with the Mouse Steroidogenic Acute Regulatory Protein Gene
Mol. Endocrinol., January 1, 2006; 20(1): 100 - 113.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Ishikawa, K. Hwang, D. Lazzarino, and P. L. Morris
Sertoli Cell Expression of Steroidogenic Acute Regulatory Protein-Related Lipid Transfer 1 and 5 Domain-Containing Proteins and Sterol Regulatory Element Binding Protein-1 Are Interleukin-1{beta} Regulated by Activation of c-Jun N-Terminal Kinase and Cyclooxygenase-2 and Cytokine Induction
Endocrinology, December 1, 2005; 146(12): 5100 - 5111.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. D. Pisarska, J. Bae, C. Klein, and A. J. W. Hsueh
Forkhead L2 Is Expressed in the Ovary and Represses the Promoter Activity of the Steroidogenic Acute Regulatory Gene
Endocrinology, July 1, 2004; 145(7): 3424 - 3433.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Sekar and J. D. Veldhuis
Involvement of Sp1 and SREBP-1a in transcriptional activation of the LDL receptor gene by insulin and LH in cultured porcine granulosa-luteal cells
Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E128 - E135.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Tajima, A. Dantes, Z. Yao, K. Sorokina, F. Kotsuji, R. Seger, and A. Amsterdam
Down-Regulation of Steroidogenic Response to Gonadotropins in Human and Rat Preovulatory Granulosa Cells Involves Mitogen-Activated Protein Kinase Activation and Modulation of DAX-1 and Steroidogenic Factor-1
J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2288 - 2299.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Z. T. Ruiz-Cortes, Y. Martel-Kennes, N. Y. Gevry, B. R. Downey, M.-F. Palin, and B. D. Murphy
Biphasic Effects of Leptin in Porcine Granulosa Cells
Biol Reprod, March 1, 2003; 68(3): 789 - 796.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. C. Nackley, W. Shea-Eaton, D. Lopez, and M. P. McLean
Repression of the Steroidogenic Acute Regulatory Gene by the Multifunctional Transcription Factor Yin Yang 1
Endocrinology, March 1, 2002; 143(3): 1085 - 1096.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. M. Stocco
Tracking the Role of a StAR in the Sky of the New Millennium
Mol. Endocrinol., August 1, 2001; 15(8): 1245 - 1254.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society