Molecular Endocrinology, Vol 7, 852-860, Copyright © 1993 by Endocrine Society

ARTICLES

Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression

Y Ikeda, DS Lala, X Luo, E Kim, MP Moisan and KL Parker
Department of Medicine, Duke University Medical Center Durham, North Carolina 27710.

The cytochrome P450 steroid hydroxylases are coordinately regulated by steroidogenic factor 1 (SF-1), a protein expressed selectively in steroidogenic cells. Based on its expression in steroidogenic tissues and DNA-binding specificity, we isolated a putative SF-1 cDNA from an adrenocortical cDNA library. As evidence that this cDNA encodes SF-1, we now show that it is selectively expressed in steroidogenic cells, that an antiserum against its protein product specifically abolishes the SF-1-related gel-shift complex, and that its coexpression increases promoter activity of the 21-hydroxylase 5'-flanking region in transfection experiments. Sequence analyses of the SF-1 cDNA revealed that it is the mouse homolog of fushi tarazu factor I (FTZ-F1), a nuclear receptor that regulates the fushi tarazu homeobox gene in Drosophila. A second FTZ-F1 homolog, embryonal long terminal repeat- binding protein (ELP), was recently isolated from embryonal carcinoma cells. SF-1 and ELP cDNAs are virtually identical for 1017 base pairs, including putative DNA-binding domains, but diverge at their 5'- and 3'- ends. One genomic clone contained both SF-1- and ELP-specific sequences, confirming their origin from a single gene. Characterization of this gene defined shared exons encoding common regions and alternative promoters and 3'-exons leading to differences between the two FTZ-F1 transcripts. We used in situ hybridization with transcript- specific probes to study the ontogeny of SF-1 and ELP expression. ELP transcripts were not detected from embryonic day 8 to adult, consistent with its previous isolation from embryonal carcinoma cells and its postulated role in early embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS)

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				N. Pilon, R. Behdjani, I. Daneau, J. G. Lussier, and D. W. Silversides Porcine Steroidogenic Factor-1 Gene (pSF-1) Expression and Analysis of Embryonic Pig Gonads during Sexual Differentiation Endocrinology, September 1, 1998; 139(9): 3803 - 3812. [Abstract] [Full Text] [PDF]

				L. M. Halvorson, M. Ito, J. L. Jameson, and W. W. Chin Steroidogenic Factor-1 and Early Growth Response Protein 1 Act through Two Composite DNA Binding Sites to Regulate Luteinizing Hormone beta -Subunit Gene Expression J. Biol. Chem., June 12, 1998; 273(24): 14712 - 14720. [Abstract] [Full Text] [PDF]

				P. A. Crawford, C. Dorn, Y. Sadovsky, and J. Milbrandt Nuclear Receptor DAX-1 Recruits Nuclear Receptor Corepressor N-CoR to Steroidogenic Factor 1 Mol. Cell. Biol., May 1, 1998; 18(5): 2949 - 2956. [Abstract] [Full Text]

				A. N. Harris and P. L. Mellon The Basic Helix-Loop-Helix, Leucine Zipper Transcription Factor, USF (Upstream Stimulatory Factor), Is a Key Regulator of SF-1 (Steroidogenic Factor-1) Gene Expression in Pituitary Gonadotrope and Steroidogenic Cells Mol. Endocrinol., May 1, 1998; 12(5): 714 - 726. [Abstract] [Full Text]

				D. Monte, F. DeWitte, and D. W. Hum Regulation of the Human P450scc Gene by Steroidogenic Factor 1 Is Mediated by CBP/p300 J. Biol. Chem., February 20, 1998; 273(8): 4585 - 4591. [Abstract] [Full Text] [PDF]

				Y. Sadovsky and P. A. Crawford Developmental and Physiologic Roles of the Nuclear Receptor Steroidogenic Factor-I in the Reproductive System Reproductive Sciences, January 1, 1998; 5(1): 6 - 12. [Abstract] [PDF]

				C. M. HAQQ and P. K. DONAHOE Regulation of Sexual Dimorphism in Mammals Physiol Rev, January 1, 1998; 78(1): 1 - 33. [Abstract] [Full Text] [PDF]

				D. L. Duval, S. E. Nelson, and C. M. Clay The Tripartite Basal Enhancer of the Gonadotropin-Releasing Hormone (GnRH) Receptor Gene Promoter Regulates Cell-Specific Expression Through a Novel GnRH Receptor Activating Sequence Mol. Endocrinol., November 1, 1997; 11(12): 1814 - 1821. [Abstract] [Full Text]

				Y. Li and L. F. Lau Adrenocorticotropic Hormone Regulates the Activities of the Orphan Nuclear Receptor Nur77 through Modulation of Phosphorylation Endocrinology, October 1, 1997; 138(10): 4138 - 4146. [Abstract] [Full Text] [PDF]

				A. Amsterdam and N. Selvaraj Control of Differentiation, Transformation, and Apoptosis in Granulosa Cells by Oncogenes, Oncoviruses, and Tumor Suppressor Genes Endocr. Rev., August 1, 1997; 18(4): 435 - 461. [Abstract] [Full Text] [PDF]

				D. S. Sem, D. R. Casimiro, S. A. Kliewer, J. Provencal, R. M. Evans, and P. E. Wright NMR Spectroscopic Studies of the DNA-binding Domain of the Monomer-binding Nuclear Orphan Receptor, Human Estrogen Related Receptor-2. THE CARBOXYL-TERMINAL EXTENSION TO THE ZINC-FINGER REGION IS UNSTRUCTURED IN THE FREE FORM OF THE PROTEIN J. Biol. Chem., July 18, 1997; 272(29): 18038 - 18043. [Abstract] [Full Text] [PDF]

				K. L. Parker and B. P. Schimmer Steroidogenic Factor 1: A Key Determinant of Endocrine Development and Function Endocr. Rev., June 1, 1997; 18(3): 361 - 377. [Abstract] [Full Text]

				S. Mesiano and R. B. Jaffe Developmental and Functional Biology of the Primate Fetal Adrenal Cortex Endocr. Rev., June 1, 1997; 18(3): 378 - 403. [Abstract] [Full Text]

				D. Liu, Y. Le Drean, M. Ekker, F. Xiong, and C. L. Hew Teleost FTZ-F1 Homolog and Its Splicing Variant Determine the Expression of the Salmon Gonadotropin II{beta} Subunit Gene Mol. Endocrinol., June 1, 1997; 11(7): 877 - 890. [Abstract] [Full Text]

				P. Zhang and S. H. Mellon Multiple Orphan Nuclear Receptors Converge to Regulate Rat P450c17 Gene Transcription: Novel Mechanisms for Orphan Nuclear Receptor Action Mol. Endocrinol., June 1, 1997; 11(7): 891 - 904. [Abstract] [Full Text]

				M. S. Ramayya, J. Zhou, T. Kino, J. H. Segars, C. A. Bondy, and G. P. Chrousos Steroidogenic Factor 1 Messenger Ribonucleic Acid Expression in Steroidogenic and Nonsteroidogenic Human Tissues: Northern Blot and in Situ Hybridization Studies J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1799 - 1806. [Abstract] [Full Text] [PDF]

				D. S. Lala, P. M. Syka, S. B. Lazarchik, D. J. Mangelsdorf, K. L. Parker, and R. A. Heyman Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols PNAS, May 13, 1997; 94(10): 4895 - 4900. [Abstract] [Full Text] [PDF]

				S. Leers-Sucheta, K.-i. Morohashi, J. I. Mason, and M. H. Melner Synergistic Activation of the Human Type II 3beta -Hydroxysteroid Dehydrogenase/Delta 5-Delta 4 Isomerase Promoter by the Transcription Factor Steroidogenic Factor-1/Adrenal 4-binding Protein and Phorbol Ester J. Biol. Chem., March 21, 1997; 272(12): 7960 - 7967. [Abstract] [Full Text] [PDF]

				D. L. Carlone and J. S. Richards Functional Interactions, Phosphorylation, and Levels of 3',5'-Cyclic Adenosine Monophosphate-Regulatory Element Binding Protein and Steroidogenic Factor-1 Mediate Hormone-Regulated and Constitutive Expression of Aromatase in Gonadal Cells Mol. Endocrinol., March 1, 1997; 11(3): 292 - 304. [Abstract] [Full Text]

				K. G. Woodson, P. A. Crawford, Y. Sadovsky, and J. Milbrandt Characterization of the Promoter of SF-1, an Orphan Nuclear Receptor Required for Adrenal and Gonadal Development Mol. Endocrinol., February 1, 1997; 11(2): 117 - 126. [Abstract] [Full Text]

				S.-J. Chou, K.-N. Lai, and B.-c. Chung Characterization of the Upstream Sequence of the Human CYP11A1 Gene for Cell Type-specific Expression J. Biol. Chem., September 6, 1996; 271(36): 22125 - 22129. [Abstract] [Full Text] [PDF]