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 Sandhoff, T. W.
Right arrow Articles by McLean, M. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sandhoff, T. W.
Right arrow Articles by McLean, M. P.
Endocrinology Vol. 139, No. 12 4820-4831
Copyright © 1998 by The Endocrine Society

ARTICLES

Transcriptional Regulation of the Rat Steroidogenic Acute Regulatory Protein Gene by Steroidogenic Factor 11

Todd W. Sandhoff, D. Buck Hales, Karen H. Hales and Mark P. McLean

Departments of Obstetrics and Gynecology (T.W.S., M.P.M.) and Biochemistry and Molecular Biology (T.W.S., M.P.M.), University of South Florida College of Medicine, Tampa, Florida 33606; and Department of Physiology and Biophysics (D.B.H., K.H.H.), University of Illinois at Chicago, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Dr. Mark P. McLean, Departments of Obstetrics and Gynecology, 4 Columbia Drive, Room 529 Tampa, Florida 33606.

Steroidogenic acute regulatory (StAR) protein is synthesized in response to tropic hormones to facilitate cholesterol transport to the inner mitochondrial membrane-bound P450 side-chain cleavage enzyme (P450scc), the first enzymatic step in the steroid hormone biosynthetic pathway. Gonadotropins activate expression of their target genes via the cAMP second messenger system. We have demonstrated that cAMP administration to rat luteal cells stimulates expression of both StAR messenger RNA and protein. Because cholesterol delivery is the first regulated step in steroidogenesis, and because StAR messenger RNA levels are increased in response to tropic hormone and cAMP stimulation, the mechanism by which tropic hormones/cAMP stimulate transcription needs to be elucidated. To this end, approximately 2.7 kb of the rat StAR promoter was isolated and sequenced. Sequence analysis revealed the presence of a TATA-like element as well as multiple regulatory motifs including steroidogenic factor 1 (SF-1) binding sites, an estrogen receptor half-site, and two AP-1 sites within the promoter region. 5'-RACE experiments determined the transcription start site to be located 82 bp upstream of the ATG translation start codon. Electrophoretic mobility shift assays and supershift analysis demonstrated SF-1 binding to three SF-1 binding sites in the rat StAR promoter with high affinity and two SF-1 binding sites with low affinity. Transfection of mouse Y1 adrenal tumor cells and human bladder carcinoma cells (HTB9s) with the rat StAR promoter demonstrated that SF-1 was able to activate transcription of the luciferase reporter gene and that the rat StAR promoter was responsive to cAMP. Nested deletions of the rat StAR promoter (1.9 kb) identified a region between -1413 and -998 that is essential for maximal activation of the rat StAR gene in HTB9 cells; however, deletion of this region does not affect responsiveness to cAMP. 5'-Deletion and site-directed mutagenesis experiments demonstrated that the SF-1 motifs identified within the rat StAR promoter (located at positions -764, -455, and -106) were sufficient to activate transcription as well as confer cAMP responsiveness to the rat StAR gene. Site-directed mutagenesis studies using the smallest promoter fragment demonstrated that the two proximal SF-1 binding sites are crucial for StAR gene transcription, both at a basal level and in response to cAMP stimulation. These studies provide novel insights into the regulation of the rat StAR gene at the transcriptional level by SF-1.




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
 J EndocrinolHome page
E. Missaghian, P. Kempna, B. Dick, A. Hirsch, R. Alikhani-Koupaei, B. Jegou, P. E Mullis, B. M Frey, and C. E Fluck
Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents
J. Endocrinol., July 1, 2009; 202(1): 99 - 109.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
P. R. Manna, M. T. Dyson, and D. M. Stocco
Regulation of the steroidogenic acute regulatory protein gene expression: present and future perspectives
Mol. Hum. Reprod., June 1, 2009; 15(6): 321 - 333.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y.-J. Chen, M.-T. Lee, H.-C. Yao, P.-W. Hsiao, F.-C. Ke, and J.-J. Hwang
Crucial Role of Estrogen Receptor-{alpha} Interaction with Transcription Coregulators in Follicle-Stimulating Hormone and Transforming Growth Factor {beta}1 Up-Regulation of Steroidogenesis in Rat Ovarian Granulosa Cells
Endocrinology, September 1, 2008; 149(9): 4658 - 4668.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
J. Castillo, B. Castellana, L. Acerete, J. V Planas, F. W Goetz, S. Mackenzie, and L. Tort
Stress-induced regulation of steroidogenic acute regulatory protein expression in head kidney of Gilthead seabream (Sparus aurata)
J. Endocrinol., February 1, 2008; 196(2): 313 - 322.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
T. Sugawara, E. Nomura, and N. Hoshi
Cholesterol sulphate affects production of steroid hormones by reducing steroidogenic acute regulatory protein level in adrenocortical cells
J. Endocrinol., December 1, 2007; 195(3): 451 - 458.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. J. Kuhl, S. M. Ross, and K. W. Gaido
CCAAT/Enhancer Binding Protein {beta}, But Not Steroidogenic Factor-1, Modulates the Phthalate-Induced Dysregulation of Rat Fetal Testicular Steroidogenesis
Endocrinology, December 1, 2007; 148(12): 5851 - 5864.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
C. Stocco, C. Telleria, and G. Gibori
The Molecular Control of Corpus Luteum Formation, Function, and Regression
Endocr. Rev., February 1, 2007; 28(1): 117 - 149.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
K. A Brown, K. Sayasith, N. Bouchard, J. G Lussier, and J. Sirois
Molecular cloning of equine 17{beta}-hydroxysteroid dehydrogenase type 1 and its downregulation during follicular luteinization in vivo
J. Mol. Endocrinol., January 1, 2007; 38(1): 67 - 78.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. V. Patchev, D. Fischer, S. S. Wolf, M. Herkenham, F. Gotz, M. Gehin, P. Chambon, V. K. Patchev, and O. F. X. Almeida
Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice
FASEB J, January 1, 2007; 21(1): 231 - 238.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
T. Sugawara, N. Sakuragi, and H. Minakami
CREM confers cAMP responsiveness in human steroidogenic acute regulatory protein expression in NCI-H295R cells rather than SF-1/Ad4BP.
J. Endocrinol., October 1, 2006; 191(1): 327 - 337.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. A. Brown, M. Dore, J. G. Lussier, and J. Sirois
Human Chorionic Gonadotropin-Dependent Up-Regulation of Genes Responsible for Estrogen Sulfoconjugation and Export in Granulosa Cells of Luteinizing Preovulatory Follicles
Endocrinology, September 1, 2006; 147(9): 4222 - 4233.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
A. J Casal, V. J P Sinclair, A. M Capponi, J. Nicod, U. Huynh-Do, and P. Ferrari
A novel mutation in the steroidogenic acute regulatory protein gene promoter leading to reduced promoter activity.
J. Mol. Endocrinol., August 1, 2006; 37(1): 71 - 80.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
K A Brown, D Boerboom, N Bouchard, M Dore, J G Lussier, and J Sirois
Human chorionic gonadotropin-dependent induction of an equine aldo-keto reductase (AKR1C23) with 20{alpha}-hydroxysteroid dehydrogenase activity during follicular luteinization in vivo.
J. Mol. Endocrinol., June 1, 2006; 36(3): 449 - 461.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. N. Winnay, J. Xu, B. W. O'Malley, and G. D. Hammer
Steroid Receptor Coactivator-1-Deficient Mice Exhibit Altered Hypothalamic-Pituitary-Adrenal Axis Function
Endocrinology, March 1, 2006; 147(3): 1322 - 1332.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. M. Naciff, K. A. Hess, G. J. Overmann, S. M. Torontali, G. J. Carr, J. P. Tiesman, L. M. Foertsch, B. D. Richardson, J. E. Martinez, and G. P. Daston
Gene Expression Changes Induced in the Testis by Transplacental Exposure to High and Low Doses of 17{alpha}-Ethynyl Estradiol, Genistein, or Bisphenol A
Toxicol. Sci., August 1, 2005; 86(2): 396 - 416.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. F. Clem, E. A. Hudson, and B. J. Clark
Cyclic Adenosine 3',5'-Monophosphate (cAMP) Enhances cAMP-Responsive Element Binding (CREB) Protein Phosphorylation and Phospho-CREB Interaction with the Mouse Steroidogenic Acute Regulatory Protein Gene Promoter
Endocrinology, March 1, 2005; 146(3): 1348 - 1356.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. P. Piekorz, S. Gingras, A. Hoffmeyer, J. N. Ihle, and Y. Weinstein
Regulation of Progesterone Levels during Pregnancy and Parturition by Signal Transducer and Activator of Transcription 5 and 20{alpha}-Hydroxysteroid Dehydrogenase
Mol. Endocrinol., February 1, 2005; 19(2): 431 - 440.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. A. LaVoie, D. Singh, and Y. Y. Hui
Concerted Regulation of the Porcine Steroidogenic Acute Regulatory Protein Gene Promoter Activity by Follicle-Stimulating Hormone and Insulin-Like Growth Factor I in Granulosa Cells Involves GATA-4 and CCAAT/Enhancer Binding Protein {beta}
Endocrinology, July 1, 2004; 145(7): 3122 - 3134.
[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
 Mol. Endocrinol.Home page
P. R. Manna, D. W. Eubank, and D. M. Stocco
Assessment of the Role of Activator Protein-1 on Transcription of the Mouse Steroidogenic Acute Regulatory Protein Gene
Mol. Endocrinol., March 1, 2004; 18(3): 558 - 573.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
N. Peng, J. W. Kim, W. E. Rainey, B. R. Carr, and G. R. Attia
The Role of the Orphan Nuclear Receptor, Liver Receptor Homologue-1, in the Regulation of Human Corpus Luteum 3{beta}-Hydroxysteroid Dehydrogenase Type II
J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6020 - 6028.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. S. Sun, K.-Y. Hsiao, C.-C. Hsu, M.-H. Wu, and S.-J. Tsai
Transactivation of Steroidogenic Acute Regulatory Protein in Human Endometriotic Stromal Cells Is Mediated by the Prostaglandin EP2 Receptor
Endocrinology, September 1, 2003; 144(9): 3934 - 3942.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
P. R. Manna, I. T. Huhtaniemi, X.-J. Wang, D. W. Eubank, and D. M. Stocco
Mechanisms of Epidermal Growth Factor Signaling: Regulation of Steroid Biosynthesis and the Steroidogenic Acute Regulatory Protein in Mouse Leydig Tumor Cells
Biol Reprod, November 1, 2002; 67(5): 1393 - 1404.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Osman, C. Murigande, A. Nadakal, and A. M. Capponi
Repression of DAX-1 and Induction of SF-1 Expression. TWO MECHANISMS CONTRIBUTING TO THE ACTIVATION OF ALDOSTERONE BIOSYNTHESIS IN ADRENAL GLOMERULOSA CELLS
J. Biol. Chem., October 18, 2002; 277(43): 41259 - 41267.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. R. Fielden, R. G. Halgren, C. J. Fong, C. Staub, L. Johnson, K. Chou, and T. R. Zacharewski
Gestational and Lactational Exposure of Male Mice to Diethylstilbestrol Causes Long-Term Effects on the Testis, Sperm Fertilizing Ability in Vitro, and Testicular Gene Expression
Endocrinology, August 1, 2002; 143(8): 3044 - 3059.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. Borud, T. Hoang, M. Bakke, A. L. Jacob, J. Lund, and G. Mellgren
The Nuclear Receptor Coactivators p300/CBP/Cointegrator-Associated Protein (p/CIP) and Transcription Intermediary Factor 2 (TIF2) Differentially Regulate PKA-Stimulated Transcriptional Activity of Steroidogenic Factor 1
Mol. Endocrinol., April 1, 2002; 16(4): 757 - 773.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
P. R. Manna, M. T. Dyson, D. W. Eubank, B. J. Clark, E. Lalli, P. Sassone-Corsi, A. J. Zeleznik, and D. M. Stocco
Regulation of Steroidogenesis and the Steroidogenic Acute Regulatory Protein by a Member of the cAMP Response-Element Binding Protein Family
Mol. Endocrinol., January 1, 2002; 16(1): 184 - 199.
[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 page
 Mol. Endocrinol.Home page
L. L. Heckert
Activation of the Rat Follicle-Stimulating Hormone Receptor Promoter by Steroidogenic Factor 1 Is Blocked by Protein Kinase A and Requires Upstream Stimulatory Factor Binding to a Proximal E Box Element
Mol. Endocrinol., May 1, 2001; 15(5): 704 - 715.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
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]

Home page
 Biol. Reprod.Home page
P. de Santa Barbara, C. Méjean, B. Moniot, M.-H. Malclès, P. Berta, and B. Boizet-Bonhoure
Steroidogenic Factor-1 Contributes to the Cyclic-Adenosine Monophosphate Down-Regulation of Human SRY Gene Expression
Biol Reprod, March 1, 2001; 64(3): 775 - 783.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
J. Levallet, P. Koskimies, N. Rahman, and I. Huhtaniemi
The Promoter of Murine Follicle-Stimulating Hormone Receptor: Functional Characterization and Regulation by Transcription Factor Steroidogenic Factor 1
Mol. Endocrinol., January 1, 2001; 15(1): 80 - 92.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
L. K. Christenson, T. F. Osborne, J. M. McAllister, and J. F. Strauss III
Conditional Response of the Human Steroidogenic Acute Regulatory Protein Gene Promoter to Sterol Regulatory Element Binding Protein-1a
Endocrinology, January 1, 2001; 142(1): 28 - 36.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Le Roy, J. Y. Li, D. M. Stocco, D. Langlois, and J. M. Saez
Regulation by Adrenocorticotropin (ACTH), Angiotensin II, Transforming Growth Factor-{beta}, and Insulin-Like Growth Factor I of Bovine Adrenal Cell Steroidogenic Capacity and Expression of ACTH Receptor, Steroidogenic Acute Regulatory Protein, Cytochrome P450c17, and 3{beta}-Hydroxysteroid Dehydrogenase
Endocrinology, May 1, 2000; 141(5): 1599 - 1607.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. R. Wooton-Kee and B. J. Clark
Steroidogenic Factor-1 Influences Protein-Deoxyribonucleic Acid Interactions within the Cyclic Adenosine 3',5'-Monophosphate-Responsive Regions of the Murine Steroidogenic Acute Regulatory Protein Gene
Endocrinology, April 1, 2000; 141(4): 1345 - 1355.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. J. Clark and R. Combs
Angiotensin II and Cyclic Adenosine 3',5'-Monophosphate Induce Human Steroidogenic Acute Regulatory Protein Transcription through a Common Steroidogenic Factor-1 Element
Endocrinology, October 1, 1999; 140(10): 4390 - 4398.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
R. Mamluk, N. Defer, J. Hanoune, and R. Meidan
Molecular Identification of Adenylyl Cyclase 3 in Bovine Corpus Luteum and Its Regulation by Prostaglandin F2{alpha}-Induced Signaling Pathways
Endocrinology, October 1, 1999; 140(10): 4601 - 4608.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
L. K. Christenson, P. F. Johnson, J. M. McAllister, and J. F. Strauss III
CCAAT/Enhancer-binding Proteins Regulate Expression of the Human Steroidogenic Acute Regulatory Protein (StAR) Gene
J. Biol. Chem., September 10, 1999; 274(37): 26591 - 26598.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. Lopez, T. W. Sandhoff, and M. P. McLean
Steroidogenic Factor-1 Mediates Cyclic 3',5'-Adenosine Monophosphate Regulation of the High Density Lipoprotein Receptor
Endocrinology, July 1, 1999; 140(7): 3034 - 3044.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
E. Silverman, S. Eimerl, and J. Orly
CCAAT Enhancer-binding Protein beta  and GATA-4 Binding Regions within the Promoter of the Steroidogenic Acute Regulatory Protein (StAR) Gene Are Required for Transcription in Rat Ovarian Cells
J. Biol. Chem., June 18, 1999; 274(25): 17987 - 17996.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. J. Reinhart, S. C. Williams, B. J. Clark, and D. M. Stocco
SF-1 (Steroidogenic Factor-1) and C/EBP{beta} (CCAAT/Enhancer Binding Protein-{beta}) Cooperate to Regulate the Murine StAR (Steroidogenic Acute Regulatory) Promoter
Mol. Endocrinol., May 1, 1999; 13(5): 729 - 741.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
T. Mizutani, K. Yamada, T. Minegishi, and K. Miyamoto
Transcriptional Regulation of Rat Scavenger Receptor Class B Type I Gene
J. Biol. Chem., July 14, 2000; 275(29): 22512 - 22519.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. E. Reyland, R. M. Evans, and E. K. White
Lipoproteins Regulate Expression of the Steroidogenic Acute Regulatory Protein (StAR) in Mouse Adrenocortical Cells
J. Biol. Chem., November 17, 2000; 275(47): 36637 - 36644.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Gizard, B. Lavallee, F. DeWitte, and D. W. Hum
A Novel Zinc Finger Protein TReP-132 Interacts with CBP/p300 to Regulate Human CYP11A1 Gene Expression
J. Biol. Chem., August 31, 2001; 276(36): 33881 - 33892.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]


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 © 1998 by The Endocrine Society