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Molecular Endocrinology, Vol 10, 1261-1272, Copyright © 1996 by Endocrine Society

ARTICLES

Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development

Y Ikeda, A Swain, TJ Weber, KE Hentges, E Zanaria, E Lalli, KT Tamai, P Sassone- Corsi, R Lovell-Badge, G Camerino and KL Parker
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Mutations of the orphan nuclear receptors, steroidogenic factor 1 (SF- 1) and DAX-1, cause complex endocrine phenotypes that include impaired adrenal development and hypogonadotrophic hypogonadism. These similar phenotypes suggest that SF-1 and DAX-1 act in the same pathway(s) of endocrine development. To explore this model, we now compare directly their sites of expression. In mouse embryos, SF-1 expression in the urogenital ridge and brain either preceded or coincided with Dax-1 expression, with coordinate expression thereafter in the adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary. The striking colocalization of SF-1 and Dax-1 supports the model that they are intimately linked in a common pathway of endocrine development. The slightly earlier onset of SF-1 expression and its ability to bind specifically to a conserved sequence in the Dax-1 5'-flanking region suggested that SF-1 may activate Dax-1 expression. However, promoter activity of Dax-1 5'-flanking sequences did not require this potential SF-1-responsive element, and Dax-1 expression was unimpaired in knockout mice lacking SF-1, establishing that SF-1 is not required for Dax-1 gene expression in these settings. Although the precise mechanisms remain to be established and may be multifactorial, our results strongly suggest that these two orphan nuclear receptors interact in a common pathway of endocrine development.


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 J. Clin. Endocrinol. Metab.Home page
S. J. B. Aylwin, J. P. Welch, C. L. Davey, J. F. Geddes, D. F. Wood, G. M. Besser, A. B. Grossman, J. P. Monson, and J. M. Burrin
The Relationship between Steroidogenic Factor 1 and DAX-1 Expression and in Vitro Gonadotropin Secretion in Human Pituitary Adenomas
J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2476 - 2483.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
S. B. Seminara and W. F. Crowley Jr.
Perspective: The Importance of Genetic Defects in Humans in Elucidating the Complexities of the Hypothalamic-Pituitary-Gonadal Axis
Endocrinology, June 1, 2001; 142(6): 2173 - 2177.
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 Biol. Reprod.Home page
J. J. Tremblay and R. S. Viger
Nuclear Receptor Dax-1 Represses the Transcriptional Cooperation Between GATA-4 and SF-1 in Sertoli Cells
Biol Reprod, April 1, 2001; 64(4): 1191 - 1199.
[Abstract] [Full Text]

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 EndocrinologyHome page
J. J. Tremblay and R. S. Viger
GATA Factors Differentially Activate Multiple Gonadal Promoters through Conserved GATA Regulatory Elements
Endocrinology, March 1, 2001; 142(3): 977 - 986.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
A. Lacroix, N. N'Diaye, J. Tremblay, and P. Hamet
Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome
Endocr. Rev., February 1, 2001; 22(1): 75 - 110.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
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]

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 Mol. Cell. Biol.Home page
E. Lalli, K. Ohe, C. Hindelang, and P. Sassone-Corsi
Orphan Receptor DAX-1 Is a Shuttling RNA Binding Protein Associated with Polyribosomes via mRNA
Mol. Cell. Biol., July 1, 2000; 20(13): 4910 - 4921.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
IMAGe, a New Clinical Association of Intrauterine Growth Retardation, Metaphyseal Dysplasia, Adrenal Hypoplasia Congenita, and Genital Anomalies
J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4335 - 4340.
[Abstract] [Full Text]

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 Endocr. Rev.Home page
V. Giguère
Orphan Nuclear Receptors: From Gene to Function
Endocr. Rev., October 1, 1999; 20(5): 689 - 725.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
M. W. Wolfe
The Equine Luteinizing Hormone {beta}-Subunit Promoter Contains Two Functional Steroidogenic Factor-1 Response Elements
Mol. Endocrinol., September 1, 1999; 13(9): 1497 - 1510.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
K. Kawabe, T. Shikayama, H. Tsuboi, S. Oka, K. Oba, T. Yanase, H. Nawata, and K.-i. Morohashi
Dax-1 as One of the Target Genes of Ad4BP/SF-1
Mol. Endocrinol., August 1, 1999; 13(8): 1267 - 1284.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
Y.-K. Lee, K. L. Parker, H.-S. Choi, and D. D. Moore
Activation of the Promoter of the Orphan Receptor SHP by Orphan Receptors That Bind DNA as Monomers
J. Biol. Chem., July 23, 1999; 274(30): 20869 - 20873.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. Dorn, Q. Ou, J. Svaren, P. A. Crawford, and Y. Sadovsky
Activation of Luteinizing Hormone beta  Gene by Gonadotropin-releasing Hormone Requires the Synergy of Early Growth Response-1 and Steroidogenic Factor-1
J. Biol. Chem., May 14, 1999; 274(20): 13870 - 13876.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
D. P. Merke, T. Tajima, J. Baron, and G. B. Cutler
Hypogonadotropic Hypogonadism in a Female Caused by an X-Linked Recessive Mutation in the DAX1 Gene
N. Engl. J. Med., April 22, 1999; 340(16): 1248 - 1252.
[Full Text] [PDF]

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 EndocrinologyHome page
P. R. Manna, P. Pakarinen, T. El-Hefnawy, and I. T. Huhtaniemi
Functional Assessment of the Calcium Messenger System in Cultured Mouse Leydig Tumor Cells: Regulation of Human Chorionic Gonadotropin-Induced Expression of the Steroidogenic Acute Regulatory Protein
Endocrinology, April 1, 1999; 140(4): 1739 - 1751.
[Abstract] [Full Text]

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 Genes Dev.Home page
A. Swain and R. Lovell-Badge
Mammalian sex determination: a molecular drama
Genes & Dev., April 1, 1999; 13(7): 755 - 767.
[Full Text]

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 J. Biol. Chem.Home page
P. R. Manna, M. Tena-Sempere, and I. T. Huhtaniemi
Molecular Mechanisms of Thyroid Hormone-stimulated Steroidogenesis in Mouse Leydig Tumor Cells. INVOLVEMENT OF THE STEROIDOGENIC ACUTE REGULATORY () PROTEIN
J. Biol. Chem., February 26, 1999; 274(9): 5909 - 5918.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
A. T. Reutens, J. C. Achermann, M. Ito, M. Ito, W.-X. Gu, R. L. Habiby, P. A. Donohoue, S. Pang, P. C. Hindmarsh, and J. L. Jameson
Clinical and Functional Effects of Mutations in the DAX-1 Gene in Patients with Adrenal Hypoplasia Congenita
J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 504 - 511.
[Abstract] [Full Text]

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 EndocrinologyHome page
E. Lalli, M. H. Melner, D. M. Stocco, and P. Sassone-Corsi
DAX-1 Blocks Steroid Production at Multiple Levels
Endocrinology, October 1, 1998; 139(10): 4237 - 4243.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
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]

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 Mol. Endocrinol.Home page
R. N. Yu, M. Ito, and J. L. Jameson
The Murine Dax-1 Promoter Is Stimulated by SF-1 (Steroidogenic Factor-1) and Inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) via a Composite Nuclear Receptor-Regulatory Element
Mol. Endocrinol., July 1, 1998; 12(7): 1010 - 1022.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
H.-K. Lee, Y.-K. Lee, S.-H. Park, Y.-S. Kim, S. H. Park, J. W. Lee, H.-B. Kwon, J. Soh, D. D. Moore, and H.-S. Choi
Structure and Expression of the Orphan Nuclear Receptor SHP Gene
J. Biol. Chem., June 5, 1998; 273(23): 14398 - 14402.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
R. Viger, C Mertineit, J. Trasler, and M Nemer
Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter
Development, January 7, 1998; 125(14): 2665 - 2675.
[Abstract] [PDF]

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 Endocr. Rev.Home page
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]

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 J. Biol. Chem.Home page
H. Zhang, J. S. Thomsen, L. Johansson, J.-A. Gustafsson, and E. Treuter
DAX-1 Functions as an LXXLL-containing Corepressor for Activated Estrogen Receptors
J. Biol. Chem., December 15, 2000; 275(51): 39855 - 39859.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
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]


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