| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Physiology, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, California 94143-0444
Address all correspondence and requests for reprints to: Holly A. Ingraham, Department of Physiology, Box 0444, University of California, San Francisco, San Francisco, California 94143-0444. E-mail: hollyi{at}itsa.ucsf.edu.
The importance of steroidogenic factor-1 (SF-1) gene dosage in endocrine function is evidenced by phenotypes associated with the heterozygous state in mice and humans. Here we examined mechanisms underlying SF-1 haploinsufficiency and found a striking reduction (12-fold) in SF-1 heterozygous (+/-) adrenocortical size at embryonic day (E) 12. Loss of one SF-1 allele led to a selective decrease in adrenal precursors within the adrenogonadal primordium at E10.0, without affecting the number of gonadal precursors, as marked by GATA-4. Beginning at E13.5, increased cell proliferation in SF-1 +/- adrenals allows these organs to approach but not attain a normal size. Remarkably, neural crest-derived adrenomedullary precursors migrated normally in SF-1 +/- and null embryos. However, later in development, medullary growth was compromised in both genotypes. Despite the small adrenal size in SF-1heterozygotes, an unexpected elevation in steroidogenic capacity per cell was observed in primary adult adrenocortical SF-1 +/- cells compared with wild-type cells. Elevated cellular steroid output is consistent with the up-regulation of some SF-1 target genes in SF-1 +/- adrenals and may partially be due to an observed increase in nerve growth factor-induced-B. Our findings underscore the need for full SF-1 gene dosage early in adrenal development, but not in the adult adrenal, where compensatory mechanisms restore near normal function.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  M. Zubair, S. Oka, K. L. Parker, and K.-i. Morohashi Transgenic Expression of Ad4BP/SF-1 in Fetal Adrenal Progenitor Cells Leads to Ectopic Adrenal Formation Mol. Endocrinol., October 1, 2009; 23(10): 1657 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yazawa, Y. Inanoka, T. Mizutani, M. Kuribayashi, A. Umezawa, and K. Miyamoto Liver Receptor Homolog-1 Regulates the Transcription of Steroidogenic Enzymes and Induces the Differentiation of Mesenchymal Stem Cells into Steroidogenic Cells Endocrinology, August 1, 2009; 150(8): 3885 - 3893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Kim, F. M. Barlaskar, J. H. Heaton, T. Else, V. R. Kelly, K. T. Krill, J. O. Scheys, D. P. Simon, A. Trovato, W.-H. Yang, et al. In Search of Adrenocortical Stem and Progenitor Cells Endocr. Rev., May 1, 2009; 30(3): 241 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zubair, K. L. Parker, and K.-i. Morohashi Developmental Links between the Fetal and Adult Zones of the Adrenal Cortex Revealed by Lineage Tracing Mol. Cell. Biol., December 1, 2008; 28(23): 7030 - 7040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gondo, T. Okabe, T. Tanaka, H. Morinaga, M. Nomura, R. Takayanagi, H. Nawata, and T. Yanase Adipose Tissue-Derived and Bone Marrow-Derived Mesenchymal Cells Develop into Different Lineage of Steroidogenic Cells by Forced Expression of Steroidogenic Factor 1 Endocrinology, September 1, 2008; 149(9): 4717 - 4725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
M.-C. Shih, N.-C. Hsu, C.-C. Huang, T.-S. Wu, P.-Y. Lai, and B.-c. Chung Mutation of Mouse Cyp11a1 Promoter Caused Tissue-Specific Reduction of Gene Expression and Blunted Stress Response without Affecting Reproduction Mol. Endocrinol., April 1, 2008; 22(4): 915 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Chen, J.-H. Weng, C.-C. Huang, and B.-c. Chung Histone Deacetylase Inhibitors Reduce Steroidogenesis through SCF-Mediated Ubiquitination and Degradation of Steroidogenic Factor 1 (NR5A1) Mol. Cell. Biol., October 15, 2007; 27(20): 7284 - 7290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Val, J.-P. Martinez-Barbera, and A. Swain Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage Development, June 15, 2007; 134(12): 2349 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Dammer, A. Leon, and M. B. Sewer Coregulator Exchange and Sphingosine-Sensitive Cooperativity of Steroidogenic Factor-1, General Control Nonderepressed 5, p54, and p160 Coactivators Regulate Cyclic Adenosine 3',5'-Monophosphate-Dependent Cytochrome P450c17 Transcription Rate Mol. Endocrinol., February 1, 2007; 21(2): 415 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. D. Lichtenauer, M. Duchniewicz, M. Kolanczyk, A. Hoeflich, S. Hahner, T. Else, A. B. Bicknell, T. Zemojtel, N. R. Stallings, D. M. Schulte, et al. Pre-B-Cell Transcription Factor 1 and Steroidogenic Factor 1 Synergistically Regulate Adrenocortical Growth and Steroidogenesis Endocrinology, February 1, 2007; 148(2): 693 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. M. Ulrich-Lai, H. F. Figueiredo, M. M. Ostrander, D. C. Choi, W. C. Engeland, and J. P. Herman Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E965 - E973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Song, Y.-Y. Park, H. J. Kee, C. Y. Hong, Y.-S. Lee, S.-W. Ahn, H.-J. Kim, K. Lee, H. Kook, I.-K. Lee, et al. Orphan Nuclear Receptor Nur77 Induces Zinc Finger Protein GIOT-1 Gene Expression, and GIOT-1 Acts as a Novel Corepressor of Orphan Nuclear Receptor SF-1 via Recruitment of HDAC2 J. Biol. Chem., June 9, 2006; 281(23): 15605 - 15614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zubair, S. Ishihara, S. Oka, K. Okumura, and K.-i. Morohashi Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1. Mol. Cell. Biol., June 1, 2006; 26(11): 4111 - 4121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shima, M. Zubair, S. Ishihara, Y. Shinohara, S. Oka, S. Kimura, S. Okamoto, Y. Minokoshi, S. Suita, and K.-i. Morohashi Ventromedial Hypothalamic Nucleus-Specific Enhancer of Ad4BP/SF-1 Gene Mol. Endocrinol., November 1, 2005; 19(11): 2812 - 2823. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gut, K. Huber, J. Lohr, B. Bruhl, S. Oberle, M. Treier, U. Ernsberger, C. Kalcheim, and K. Unsicker Lack of an adrenal cortex in Sf1 mutant mice is compatible with the generation and differentiation of chromaffin cells Development, October 15, 2005; 132(20): 4611 - 4619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. B. Lee, L. A. Lebedeva, M. Suzawa, S. A. Wadekar, M. Desclozeaux, and H. A. Ingraham The DEAD-Box Protein DP103 (Ddx20 or Gemin-3) Represses Orphan Nuclear Receptor Activity via SUMO Modification Mol. Cell. Biol., March 1, 2005; 25(5): 1879 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Hammer, K. L. Parker, and B. P. Schimmer Minireview: Transcriptional Regulation of Adrenocortical Development Endocrinology, March 1, 2005; 146(3): 1018 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Jameson Of Mice and Men: The Tale of Steroidogenic Factor-1 J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5927 - 5929. [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Song, Y.-Y. Park, K. C. Park, C. Y. Hong, J. H. Park, M. Shong, K. Lee, and H.-S. Choi The Atypical Orphan Nuclear Receptor DAX-1 Interacts with Orphan Nuclear Receptor Nur77 and Represses Its Transactivation Mol. Endocrinol., August 1, 2004; 18(8): 1929 - 1940. [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 |
