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 Zimmermann, S. Articles by Adham, I. M. Search for Related Content PubMed PubMed Citation Articles by Zimmermann, S. Articles by Adham, I. M.

Transcription of the Leydig Insulin-Like Gene Is Mediated by Steroidogenic Factor-1

Institute of Human Genetics University of Göttingen 37073 Göttingen, Germany

The Leydig insulin-like gene (Ley I-L), a member of the insulin-related gene family, is specifically expressed in pre- and postnatal Leydig cells of the testis and in postnatal theca cells of the ovary. To determine the functional region of the mouse Ley I-L promoter and factors controlling the Ley I-L gene expression, we used 2.1 kb of the 5'-flanking region of the mouse Ley I-L gene to generate chimeric constructs with the chloramphenicol acetyltransferase gene (CAT). Transient transfections of MA10 Leydig cells, LTK^- fibroblasts, and F9 embryonic cells by a series of 5'-deleted mouse Ley I-L promoter-CAT constructs revealed that the sequence between nucleotides -157 to +4 directs the transcription of the reporter gene in MA10 but not in LTK^- and F9 cells, indicating that the determinants of Leydig cell-specific expression reside within this region. Deoxyribonuclease I (DNase I) footprint analysis revealed that the sequences designated SF-1/1, SF-1/2, and SF-1/3 within three DNase I-protected regions are homologous to the consensus binding site of the steroidogenic factor-1 (SF-1). Competition and antibody studies showed that the three SF-1-binding sites in the Ley I-L promoter have similar binding affinities for SF-1. Furthermore, transient transfections of MA10 cells with mutant reporter constructs, in which SF-1/1 or both SF-1/2 and SF-1/3 were deleted, demonstrated that all three SF-1- binding sites are required for SF-1-mediated stimulation of Ley I-L transcription. Cotransfection of an SF-1-containing expression vector together with a Ley I-L promoter-CAT construct into HeLa cells, which lack the endogenous SF-1 protein, resulted in CAT gene transcription, which indicated that SF-1 can transactivate the Ley I-L promoter. These data demonstrate an essential role of SF-1 in transcriptional activation of the Ley I-L promoter.

This article has been cited by other articles:

				R. Ivell and R. Anand-Ivell Biology of insulin-like factor 3 in human reproduction Hum. Reprod. Update, July 1, 2009; 15(4): 463 - 476. [Abstract] [Full Text] [PDF]

				T. Ventura, R. Manor, E. D. Aflalo, S. Weil, S. Raviv, L. Glazer, and A. Sagi Temporal Silencing of an Androgenic Gland-Specific Insulin-Like Gene Affecting Phenotypical Gender Differences and Spermatogenesis Endocrinology, March 1, 2009; 150(3): 1278 - 1286. [Abstract] [Full Text] [PDF]

				E. Lague and J. J. Tremblay Antagonistic Effects of Testosterone and the Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate on INSL3 Transcription in Leydig Cells Endocrinology, September 1, 2008; 149(9): 4688 - 4694. [Abstract] [Full Text] [PDF]

				C. R. Cederroth, O. Schaad, P. Descombes, P. Chambon, J.-D. Vassalli, and S. Nef Estrogen Receptor {alpha} Is a Major Contributor to Estrogen-Mediated Fetal Testis Dysgenesis and Cryptorchidism Endocrinology, November 1, 2007; 148(11): 5507 - 5519. [Abstract] [Full Text] [PDF]

				S. Feng, N. V Bogatcheva, A. Truong, B. Korchin, C. E Bishop, T. Klonisch, I. U Agoulnik, and A. I Agoulnik Developmental Expression and Gene Regulation of Insulin-like 3 Receptor RXFP2 in Mouse Male Reproductive Organs Biol Reprod, October 1, 2007; 77(4): 671 - 680. [Abstract] [Full Text] [PDF]

				G. De Rienzo, F. Aniello, M. Branno, G. Izzo, and S. Minucci The expression level of frog relaxin mRNA (fRLX), in the testis of Rana esculenta, is influenced by testosterone J. Exp. Biol., October 1, 2006; 209(19): 3806 - 3811. [Abstract] [Full Text] [PDF]

				N. M. Robert, L. J. Martin, and J. J. Tremblay The Orphan Nuclear Receptor NR4A1 Regulates Insulin-Like 3 Gene Transcription in Leydig Cells Biol Reprod, February 1, 2006; 74(2): 322 - 330. [Abstract] [Full Text] [PDF]

				A. Truong, N. V. Bogatcheva, C. Schelling, G. Dolf, and A. I. Agoulnik Isolation and Expression Analysis of the Canine Insulin-Like Factor 3 Gene Biol Reprod, November 1, 2003; 69(5): 1658 - 1664. [Abstract] [Full Text] [PDF]

				T. Klonisch, K. Steger, A. Kehlen, W. R. Allen, C. Froehlich, J. Kauffold, M. Bergmann, and S. Hombach-Klonisch INSL3 Ligand-Receptor System in the Equine Testis Biol Reprod, June 1, 2003; 68(6): 1975 - 1981. [Abstract] [Full Text] [PDF]

				R. Ivell and S. Hartung The molecular basis of cryptorchidism Mol. Hum. Reprod., April 1, 2003; 9(4): 175 - 181. [Abstract] [Full Text] [PDF]

				R. Ivell and R. A.D. Bathgate Reproductive Biology of the Relaxin-Like Factor (RLF/INSL3) Biol Reprod, September 1, 2002; 67(3): 699 - 705. [Abstract] [Full Text] [PDF]

				J. H.-C. Shen and H. A. Ingraham Regulation of the Orphan Nuclear Receptor Steroidogenic Factor 1 by Sox Proteins Mol. Endocrinol., March 1, 2002; 16(3): 529 - 540. [Abstract] [Full Text] [PDF]

				P. Koskimies, J. Levallet, P. Sipila, I. Huhtaniemi, and M. Poutanen Murine Relaxin-Like Factor Promoter: Functional Characterization and Regulation by Transcription Factors Steroidogenic Factor 1 and DAX-1 Endocrinology, March 1, 2002; 143(3): 909 - 919. [Abstract] [Full Text] [PDF]

				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]

				G. de Rienzo, F. Aniello, M. Branno, and S. Minucci Isolation and Characterization of a Novel Member of the Relaxin/Insulin Family from the Testis of the Frog Rana esculenta Endocrinology, July 1, 2001; 142(7): 3231 - 3238. [Abstract] [Full Text] [PDF]

				Z. J. Wang, B. Jeffs, M. Ito, J. C. Achermann, R. N. Yu, D. B. Hales, and J. L. Jameson Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1 PNAS, June 20, 2001; (2001) 141543298. [Abstract] [Full Text] [PDF]

				L. O'Donnell, K. M. Robertson, M. E. Jones, and E. R. Simpson Estrogen and Spermatogenesis Endocr. Rev., June 1, 2001; 22(3): 289 - 318. [Abstract] [Full Text] [PDF]

				T. Klonisch, J. Kauffold, K. Steger, M. Bergmann, R. Leiser, B. Fischer, and S. Hombach-Klonisch Canine Relaxin-Like Factor: Unique Molecular Structure and Differential Expression Within Reproductive Tissues of the Dog Biol Reprod, February 1, 2001; 64(2): 442 - 450. [Abstract] [Full Text]

				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]

				D. Boerboom, N. Pilon, R. Behdjani, D. W. Silversides, and J. Sirois Expression and Regulation of Transcripts Encoding Two Members of the NR5A Nuclear Receptor Subfamily of Orphan Nuclear Receptors, Steroidogenic Factor-1 and NR5A2, in Equine Ovarian Cells during the Ovulatory Process Endocrinology, December 1, 2000; 141(12): 4647 - 4656. [Abstract] [Full Text] [PDF]

				M. Tomboc, P. A. Lee, M. F. Mitwally, F. X. Schneck, M. Bellinger, and S. F. Witchel Insulin-like 3/Relaxin-Like Factor Gene Mutations Are Associated with Cryptorchidism J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4013 - 4018. [Abstract] [Full Text]

				C. Krausz, L. Quintana-Murci, M. Fellous, J.-P. Siffroi, and K. McElreavey Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism Mol. Hum. Reprod., April 1, 2000; 6(4): 298 - 302. [Abstract] [Full Text] [PDF]

				E. E. Bullesbach and C. Schwabe Specific, High Affinity Relaxin-like Factor Receptors J. Biol. Chem., August 6, 1999; 274(32): 22354 - 22358. [Abstract] [Full Text] [PDF]

				K.-i. Morohashi, H. Tsuboi-Asai, S. Matsushita, M. Suda, M. Nakashima, H. Sasano, Y. Hataba, C.-L. Li, J. Fukata, J. Irie, et al. Structural and Functional Abnormalities in the Spleen of an mFtz-F1 Gene-Disrupted Mouse Blood, March 1, 1999; 93(5): 1586 - 1594. [Abstract] [Full Text] [PDF]

				P. d. S. Barbara, B. Moniot, F. Poulat, B. Boizet, and P. Berta Steroidogenic Factor-1 Regulates Transcription of the Human Anti-mullerian Hormone Receptor J. Biol. Chem., November 6, 1998; 273(45): 29654 - 29660. [Abstract] [Full Text] [PDF]

				Z. J. Wang, B. Jeffs, M. Ito, J. C. Achermann, R. N. Yu, D. B. Hales, and J. L. Jameson Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1 PNAS, July 3, 2001; 98(14): 7988 - 7993. [Abstract] [Full Text] [PDF]