help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Molecular Endocrinology, doi:10.1210/me.2003-0404
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 NURSA Molecule Pages Link
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 Jeyasuria, P.
Right arrow Articles by Parker, K. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeyasuria, P.
Right arrow Articles by Parker, K. L.
Molecular Endocrinology 18 (7): 1610-1619
Copyright © 2004 by The Endocrine Society

Cell-Specific Knockout of Steroidogenic Factor 1 Reveals Its Essential Roles in Gonadal Function

Pancharatnam Jeyasuria, Yayoi Ikeda, Soazik P. Jamin, Liping Zhao, Dirk G. de Rooij, Axel P. N. Themmen, Richard R. Behringer and Keith L. Parker

Departments of Internal Medicine and Pharmacology (P.J., L.Z., K.L.P.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-8857; Department of Fine Morphology (Y.I.), Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; Department of Molecular Genetics (S.P.J., R.R.B.), M. D. Anderson Cancer Center, Houston, Texas 77030; Departments of Endocrinology and Cell Biology (D.G.d.R.), Utrecht University Faculty of Biology and University Medical Center, Padualaan, Utrecht 3584 CH, The Netherlands; and Department of Internal Medicine (A.P.N.T.), Erasmus University, Rotterdam 3000 DR, The Netherlands

Address all correspondence and requests for reprints to: Dr. Keith L. Parker, University of Texas Southwestern Medical Center, Room J6.106, Dallas, Texas 75390-8857. E-mail: keith.parker{at}utsouthwestern.edu.

Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a compound endocrine phenotype that includes adrenal and gonadal agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To inactivate a conditional SF-1 allele in the gonads, we targeted the expression of Cre recombinase with a knock-in allele of the anti-Müllerian hormone type 2 receptor locus. In testes, Cre was expressed in Leydig cells. The testes of adult gonad-specific SF-1 KO mice remained at the level of the bladder and were markedly hypoplastic, due at least partly to impaired spermatogenesis. Histological abnormalities of the testes were seen from early developmental stages and were associated with markedly decreased Leydig cell expression of two essential components of testosterone biosynthesis, Cyp11a and the steroidogenic acute regulatory protein. In females, the anti-Müllerian hormone type 2 receptor-Cre allele directed Cre expression to granulosa cells. Although wild-type and SF-1 KO ovaries were indistinguishable during embryogenesis and at birth, adult females were sterile and their ovaries lacked corpora lutea and contained hemorrhagic cysts resembling those in estrogen receptor {alpha} and aromatase KO mice. Collectively, these studies establish definitively that SF-1 expression in the gonads is essential for normal reproductive development and function.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1



This article has been cited by other articles:


Home page
 Endocr. Rev.Home page
M. A. Edson, A. K. Nagaraja, and M. M. Matzuk
The Mammalian Ovary from Genesis to Revelation
Endocr. Rev., October 1, 2009; 30(6): 624 - 712.
[Abstract] [Full Text] [PDF]

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
J. A. Hernandez Gifford, M. E. Hunzicker-Dunn, and J. H. Nilson
Conditional Deletion of Beta-Catenin Mediated by Amhr2cre in Mice Causes Female Infertility
Biol Reprod, June 1, 2009; 80(6): 1282 - 1292.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. Lourenco, R. Brauner, L. Lin, A. De Perdigo, G. Weryha, M. Muresan, R. Boudjenah, G. Guerra-Junior, A. T. Maciel-Guerra, J. C. Achermann, et al.
Mutations in NR5A1 Associated with Ovarian Insufficiency
N. Engl. J. Med., March 19, 2009; 360(12): 1200 - 1210.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. R. Manna, M. T. Dyson, Y. Jo, and D. M. Stocco
Role of Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X Chromosome, Gene 1 in Protein Kinase A- and Protein Kinase C-Mediated Regulation of the Steroidogenic Acute Regulatory Protein Expression in Mouse Leydig Tumor Cells: Mechanism of Action
Endocrinology, January 1, 2009; 150(1): 187 - 199.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
X. Hong, L. J. Luense, L. K. McGinnis, W. B. Nothnick, and L. K. Christenson
Dicer1 Is Essential for Female Fertility and Normal Development of the Female Reproductive System
Endocrinology, December 1, 2008; 149(12): 6207 - 6212.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. Pelusi, Y. Ikeda, M. Zubair, and K. L. Parker
Impaired Follicle Development and Infertility in Female Mice Lacking Steroidogenic Factor 1 in Ovarian Granulosa Cells
Biol Reprod, December 1, 2008; 79(6): 1074 - 1083.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. K. Nagaraja, C. Andreu-Vieyra, H. L. Franco, L. Ma, R. Chen, D. Y. Han, H. Zhu, J. E. Agno, P. H. Gunaratne, F. J. DeMayo, et al.
Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility
Mol. Endocrinol., October 1, 2008; 22(10): 2336 - 2352.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
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]

Home page
 Biol. Reprod.Home page
A. Boyer, L. Hermo, M. Paquet, B. Robaire, and D. Boerboom
Seminiferous Tubule Degeneration and Infertility in Mice with Sustained Activation of WNT/CTNNB1 Signaling in Sertoli Cells
Biol Reprod, September 1, 2008; 79(3): 475 - 485.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. C. Kim, A. L. Reuter, M. Zubair, T. Else, K. Serecky, N. C. Bingham, G. G. Lavery, K. L. Parker, and G. D. Hammer
Targeted disruption of {beta}-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex
Development, August 1, 2008; 135(15): 2593 - 2602.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. A. Pangas, X. Li, L. Umans, A. Zwijsen, D. Huylebroeck, C. Gutierrez, D. Wang, J. F. Martin, S. P. Jamin, R. R. Behringer, et al.
Conditional Deletion of Smad1 and Smad5 in Somatic Cells of Male and Female Gonads Leads to Metastatic Tumor Development in Mice
Mol. Cell. Biol., January 1, 2008; 28(1): 248 - 257.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
P. Philibert, D. Zenaty, L. Lin, S. Soskin, F. Audran, J. Leger, J. C. Achermann, and C. Sultan
Mutational analysis of steroidogenic factor 1 (NR5a1) in 24 boys with bilateral anorchia: a French collaborative study
Hum. Reprod., December 1, 2007; 22(12): 3255 - 3261.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Andreu-Vieyra, R. Chen, and M. M. Matzuk
Effects of Granulosa Cell-Specific Deletion of Rb in Inha-{alpha} Null Female Mice
Endocrinology, August 1, 2007; 148(8): 3837 - 3849.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. Labelle-Dumais, J.-F. Pare, L. Belanger, R. Farookhi, and D. Dufort
Impaired Progesterone Production in Nr5a2+/ Mice Leads to a Reduction in Female Reproductive Function
Biol Reprod, August 1, 2007; 77(2): 217 - 225.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Sher, N. Yivgi-Ohana, and J. Orly
Transcriptional Regulation of the Cholesterol Side Chain Cleavage Cytochrome P450 Gene (CYP11A1) Revisited: Binding of GATA, Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activating Protein (AP)-1 Proteins to a Distal Novel Cluster of cis-Regulatory Elements Potentiates AP-2 and Steroidogenic Factor-1-Dependent Gene Expression in the Rodent Placenta and Ovary
Mol. Endocrinol., April 1, 2007; 21(4): 948 - 962.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Lin, P. Philibert, B. Ferraz-de-Souza, D. Kelberman, T. Homfray, A. Albanese, V. Molini, N. J. Sebire, S. Einaudi, G. S. Conway, et al.
Heterozygous Missense Mutations in Steroidogenic Factor 1 (SF1/Ad4BP, NR5A1) Are Associated with 46,XY Disorders of Sex Development with Normal Adrenal Function
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 991 - 999.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws
Ovarian follicle development and transgenic mouse models
Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. A. Pangas, X. Li, E. J. Robertson, and M. M. Matzuk
Premature Luteinization and Cumulus Cell Defects in Ovarian-Specific Smad4 Knockout Mice
Mol. Endocrinol., June 1, 2006; 20(6): 1406 - 1422.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Weck and K. E. Mayo
Switching of NR5A Proteins Associated with the Inhibin {alpha}-Subunit Gene Promoter after Activation of the Gene in Granulosa Cells
Mol. Endocrinol., May 1, 2006; 20(5): 1090 - 1103.
[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
 ReproductionHome page
A. Roy and M. M Matzuk
Deconstructing mammalian reproduction: using knockouts to define fertility pathways
Reproduction, February 1, 2006; 131(2): 207 - 219.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
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]

Home page
 Endocr. Rev.Home page
Genetically Modified Animals in Endocrinology
Endocr. Rev., December 1, 2005; 26(7): 985 - 993.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Y. Park, J. J. Meeks, G. Raverot, L. E. Pfaff, J. Weiss, G. D. Hammer, and J. L. Jameson
Nuclear receptors Sf1 and Dax1 function cooperatively to mediate somatic cell differentiation during testis development
Development, May 15, 2005; 132(10): 2415 - 2423.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Y. Park and J. L. Jameson
Minireview: Transcriptional Regulation of Gonadal Development and Differentiation
Endocrinology, March 1, 2005; 146(3): 1035 - 1042.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. J. Wilson, P. Jeyasuria, K. L. Parker, and P. Koopman
The Transcription Factors Steroidogenic Factor-1 and SOX9 Regulate Expression of Vanin-1 during Mouse Testis Development
J. Biol. Chem., February 18, 2005; 280(7): 5917 - 5923.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Z.-J. Lan, X. Xu, and A. J. Cooney
Differential Oocyte-Specific Expression of Cre Recombinase Activity in GDF-9-iCre, Zp3cre, and Msx2Cre Transgenic Mice
Biol Reprod, November 1, 2004; 71(5): 1469 - 1474.
[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 © 2004 by The Endocrine Society