| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 30, 2004
Accepted on November 15, 2004
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, Leiden University, Leiden, The Netherlands; Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands; Division of Nephrology, Department of Medicine, University of California, San Francisco, USA
* To whom correspondence should be addressed. E-mail: o.meijer{at}lacdr.leidenuniv.nl.
The mechanisms of receptor and cell-specific effects of the adrenal corticosteroid hormones via mineralo (MR) and glucocorticoid receptors (GRs) are still poorly understood. Because the expression levels of two splice variants of the steroid receptor coactivator-1, SRC-1 1a and 1e, can differ significantly in certain cell populations, we have tested the hypothesis that their relative abundance could determine cell - and receptor specific effects of corticosteroid receptor-mediated transcription.
In transient transfections, we demonstrate three novel types of SRC-1a and SRC-1e specific effects for corticosteroid receptors. (i) Promoter-dependence: SRC-1e much more potently coactivated transcription from several multiple response-element containing promoters. Mammalian 1-hydrid studies indicated that this likely does not involve promoter specific coactivator recruitment. Endogenous PNMT mRNA induction via GR was also differentially affected by the splice variants. (ii) Receptor specificity: responses mediated by the N terminal part of the MR, but not of the GR, were augmented by SRC-1e at synergizing response elements. SRC fragment SRC988-1240 by the MR-, but not the GR N terminal fragment in a 1-hybrid assay. (iii) For GR, ligand dependence: due to effects on partial agonism of RU486-activated GRs, different ratios of SRC-1a and 1e can lead to large differences in the extent of antagonism of RU486 on GR-mediated transcription.
Furthermore, we show that SRC-1e but not SRC-1a mRNA expression was regulated in the pituitary by corticosterone. We conclude that the cellular differences in SRC-1a:SRC-1e ratio demonstrated in vivo may be involved in cell specific responses to corticosteroids in a promoter and ligand-dependent way.
This article has been cited by other articles:
 |
|
 |
|
  C. P. Fitzsimons, S. Ahmed, C. F. W. Wittevrongel, T. G. Schouten, T. F. Dijkmans, W. J. J. M. Scheenen, M. J. M. Schaaf, E. Ronald de Kloet, and E. Vreugdenhil The Microtubule-Associated Protein Doublecortin-Like Regulates the Transport of the Glucocorticoid Receptor in Neuronal Progenitor Cells Mol. Endocrinol., February 1, 2008; 22(2): 248 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. van der Laan, S. B. Lachize, E. Vreugdenhil, E. R. de Kloet, and O. C. Meijer Nuclear Receptor Coregulators Differentially Modulate Induction and Glucocorticoid Receptor-Mediated Repression of the Corticotropin-Releasing Hormone Gene Endocrinology, February 1, 2008; 149(2): 725 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Newton and N. S. Holden Separating Transrepression and Transactivation: A Distressing Divorce for the Glucocorticoid Receptor? Mol. Pharmacol., October 1, 2007; 72(4): 799 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. DeRijk, S. Wust, O. C. Meijer, M.-C. Zennaro, I. S. Federenko, D. H. Hellhammer, G. Giacchetti, E. Vreugdenhil, F. G. Zitman, and E. R. de Kloet A Common Polymorphism in the Mineralocorticoid Receptor Modulates Stress Responsiveness J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5083 - 5089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Baldwin, K.-W. Huh, and K. Munger Human papillomavirus e7 oncoprotein dysregulates steroid receptor coactivator 1 localization and function. J. Virol., July 1, 2006; 80(13): 6669 - 6677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Grenier, A. Trousson, A. Chauchereau, J. Cartaud, M. Schumacher, and C. Massaad Differential Recruitment of p160 Coactivators by Glucocorticoid Receptor between Schwann Cells and Astrocytes Mol. Endocrinol., February 1, 2006; 20(2): 254 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Russcher, P. Smit, E. F. C. van Rossum, E. L. T. van den Akker, A. O. Brinkmann, L. J. M. de Heide, F. H. de Jong, J. W. Koper, and S. W. J. Lamberts Strategies for the Characterization of Disorders in Cortisol Sensitivity J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 694 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pascual-Le Tallec and M. Lombes The Mineralocorticoid Receptor: A Journey Exploring Its Diversity and Specificity of Action Mol. Endocrinol., September 1, 2005; 19(9): 2211 - 2221. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
