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 Delany, A. M. Articles by Canalis, E. Search for Related Content PubMed PubMed Citation Articles by Delany, A. M. Articles by Canalis, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE Medline Plus Health Information Steroids

Glucocorticoid Suppression of IGF I Transcription in Osteoblasts

From the Department of Research (A.M.D., D.D., E.C.), Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105; and The University of Connecticut School of Medicine (A.M.D., E.C.), Farmington, Connecticut 06030

Address all correspondence and requests for reprints to: Anne M. Delany, Ph.D., Department of Research, Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, Connecticut 06105-1299. E-Mail: adelany@stfranciscare.org.

Glucocorticoids have profound effects on bone formation, decreasing IGF I transcription in osteoblasts, but the mechanisms involved are poorly understood. We previously showed that the bp +34 to +192 region of the rat IGF I exon 1 promoter was responsible for repression of IGF I transcription by cortisol in cultures of osteoblasts from fetal rat calvariae (Ob cells). Here, site-directed mutagenesis was used to show that a binding site for members of the CAAT/enhancer binding protein family of transcription factors, within the +132 to +158 region of the promoter, mediates this glucocorticoid effect. EMSAs demonstrated that cortisol increased binding of osteoblast nuclear proteins to the +132 to +158 region of the IGF I promoter. Supershift assays showed that CAAT/enhancer binding protein , ß, and interact with this sequence, and binding of CAAT/enhancer binding protein , in particular, was increased in the presence of cortisol. Northern blot analysis showed that CAAT/enhancer binding protein and ß transcripts were increased by cortisol in Ob cells. Further, cortisol increased the transcription of these genes and increased the stability of CAAT/enhancer binding protein mRNA. In conclusion, cortisol represses IGF I transcription in osteoblasts, and CAAT/enhancer binding proteins appear to play a role in this effect.

This article has been cited by other articles:

				N. E. Schlabritz-Loutsevitch, J. C. Lopez-Alvarenga, A. G. Comuzzie, M. M. Miller, S. P. Ford, C. Li, G. B. Hubbard, R. J. Ferry Jr, and P. W. Nathanielsz The Prolonged Effect of Repeated Maternal Glucocorticoid Exposure on the Maternal and Fetal Leptin/Insulin-like Growth Factor Axis in Papio species Reproductive Sciences, March 1, 2009; 16(3): 308 - 319. [Abstract] [PDF]

				A. Giustina, G. Mazziotti, and E. Canalis Growth Hormone, Insulin-Like Growth Factors, and the Skeleton Endocr. Rev., August 1, 2008; 29(5): 535 - 559. [Abstract] [Full Text] [PDF]

				Y. Wu, W. Zhao, J. Zhao, J. Pan, Q. Wu, Y. Zhang, W. A. Bauman, and C. P. Cardozo Identification of Androgen Response Elements in the Insulin-Like Growth Factor I Upstream Promoter Endocrinology, June 1, 2007; 148(6): 2984 - 2993. [Abstract] [Full Text] [PDF]

				F.-S. Wang, C.-L. Lin, Y.-J. Chen, C.-J. Wang, K. D. Yang, Y.-T. Huang, Y.-C. Sun, and H.-C. Huang Secreted Frizzled-Related Protein 1 Modulates Glucocorticoid Attenuation of Osteogenic Activities and Bone Mass Endocrinology, May 1, 2005; 146(5): 2415 - 2423. [Abstract] [Full Text] [PDF]

				M.-F. Iu, H. Kaji, H. Sowa, J. Naito, T. Sugimoto, and K. Chihara Dexamethasone suppresses Smad3 pathway in osteoblastic cells J. Endocrinol., April 1, 2005; 185(1): 131 - 138. [Abstract] [Full Text] [PDF]

				M. Eijken, M. Hewison, M. S. Cooper, F. H. de Jong, H. Chiba, P. M. Stewart, A. G. Uitterlinden, H. A. P. Pols, and J. P. T. M. van Leeuwen 11{beta}-Hydroxysteroid Dehydrogenase Expression and Glucocorticoid Synthesis Are Directed by a Molecular Switch during Osteoblast Differentiation Mol. Endocrinol., March 1, 2005; 19(3): 621 - 631. [Abstract] [Full Text] [PDF]

				P. Dhawan, X. Peng, A. L. M. Sutton, P. N. MacDonald, C. M. Croniger, C. Trautwein, M. Centrella, T. L. McCarthy, and S. Christakos Functional Cooperation between CCAAT/Enhancer-Binding Proteins and the Vitamin D Receptor in Regulation of 25-Hydroxyvitamin D3 24-Hydroxylase Mol. Cell. Biol., January 1, 2005; 25(1): 472 - 487. [Abstract] [Full Text] [PDF]

				M. Koutsilieris, C. S. Mitsiades, J. Bogdanos, T. Dimopoulos, D. Karamanolakis, C. Milathianakis, and A. Tsintavis Combination of Somatostatin Analog, Dexamethasone, and Standard Androgen Ablation Therapy in Stage D3 Prostate Cancer Patients with Bone Metastases Clin. Cancer Res., July 1, 2004; 10(13): 4398 - 4405. [Abstract] [Full Text] [PDF]

				R. C. Pereira, A. M. Delany, and E. Canalis CCAAT/Enhancer Binding Protein Homologous Protein (DDIT3) Induces Osteoblastic Cell Differentiation Endocrinology, April 1, 2004; 145(4): 1952 - 1960. [Abstract] [Full Text] [PDF]

				M. Sciaudone, E. Gazzerro, L. Priest, A. M. Delany, and E. Canalis Notch 1 Impairs Osteoblastic Cell Differentiation Endocrinology, December 1, 2003; 144(12): 5631 - 5639. [Abstract] [Full Text] [PDF]

				A. M. Delany, I. Kalajzic, A. D. Bradshaw, E. H. Sage, and E. Canalis Osteonectin-Null Mutation Compromises Osteoblast Formation, Maturation, and Survival Endocrinology, June 1, 2003; 144(6): 2588 - 2596. [Abstract] [Full Text] [PDF]

				E. Canalis, A. N. Economides, and E. Gazzerro Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton Endocr. Rev., April 1, 2003; 24(2): 218 - 235. [Abstract] [Full Text] [PDF]

				E. Canalis and A. Giustina Glucocorticoid-Induced Osteoporosis: Summary of a Workshop J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5681 - 5685. [Full Text] [PDF]