Endocrinology, Vol 136, 33-38, Copyright © 1995 by Endocrine Society

ARTICLES

Regulation of insulin-like growth factor I transcription by prostaglandin E2 in osteoblast cells

JM Pash, AM Delany, ML Adamo, CT Roberts Jr, D LeRoith and E Canalis
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.

Insulin-like growth factor I (IGF-I) is a widely expressed abundant autocrine and paracrine factor that regulates the proliferation and differentiation of a variety of cell types. Prostaglandin E2 (PGE2) is a potent stimulator of IGF-I synthesis in bone. We examined the regulation of IGF-I synthesis by PGE2 in osteoblast-enriched (Ob) cells from fetal rat calvaria. PGE2 treatment of Ob cells at 1 microM for 2 h resulted in a 5-fold increase in heterogeneous nuclear RNA levels, as measured by a reverse transcriptase-polymerase chain reaction assay, suggesting an increase in IGF-I gene transcription. RNase protection analysis was used to map the transcriptional start sites in the IGF-I gene that are used in Ob cells. Consistent with other extrahepatic tissues, initiation of transcription occurs primarily at three sites within the 5'-regions of exon 1 of the IGF-I gene. PGE2 treatment did not alter start site usage. The regions upstream of these transcriptional start sites were analyzed by transiently transfecting Ob cells with putative rat IGF-I promoter sequences ligated to a luciferase reporter gene. Constructs containing 1.4 kilobases of the 5'- regions regions of exons 1 and 2 had significant promoter activity. PGE2 treatment of transfected Ob cells increased luciferase activity 5- fold when a 1.4-kilobase exon 1 promoter fragment was tested. This increase in luciferase activity was time and dose dependent. Smaller regions of the exon 1 promoter sequence gave higher basal activity and were less responsive to PGE2. We conclude that regions involved in IGF- I regulation by PGE2 are contained within the IGF-I promoter.

This article has been cited by other articles:

				M. Granado, A. I Martin, M{a} A. Villanua, and A. Lopez-Calderon Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1656 - E1665. [Abstract] [Full Text] [PDF]

				M. W. Wynes and D. W. H. Riches Transcription of macrophage IGF-I exon 1 is positively regulated by the 5'-untranslated region and negatively regulated by the 5'-flanking region Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1089 - L1098. [Abstract] [Full Text] [PDF]

				M. KJAeR Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading Physiol Rev, April 1, 2004; 84(2): 649 - 698. [Abstract] [Full Text] [PDF]

				G. E. McCall, D. L. Allen, F. Haddad, and K. M. Baldwin Transcriptional regulation of IGF-I expression in skeletal muscle Am J Physiol Cell Physiol, October 1, 2003; 285(4): C831 - C839. [Abstract] [Full Text] [PDF]

				A. M. Delany, D. Durant, and E. Canalis Glucocorticoid Suppression of IGF I Transcription in Osteoblasts Mol. Endocrinol., October 1, 2001; 15(10): 1781 - 1789. [Abstract] [Full Text] [PDF]

				T. E. Johnson, R. Vogel, S. J. Rutledge, G. Rodan, and A. Schmidt Thiazolidinedione Effects on Glucocorticoid Receptor-Mediated Gene Transcription and Differentiation in Osteoblastic Cells Endocrinology, July 1, 1999; 140(7): 3245 - 3254. [Abstract] [Full Text]

				M. E. Martinez, D. Heddens, D. L. Earnest, C. L. Bogert, D. Roe, J. Einspahr, J. R. Marshall, and D. S. Alberts Physical Activity, Body Mass Index, and Prostaglandin E2 Levels in Rectal Mucosa J Natl Cancer Inst, June 2, 1999; 91(11): 950 - 953. [Abstract] [Full Text] [PDF]

				Y. Umayahara, J. Billiard, C. Ji, M. Centrella, T. L. McCarthy, and P. Rotwein CCAAT/Enhancer-binding Protein delta  Is a Critical Regulator of Insulin-like Growth Factor-I Gene Transcription in Osteoblasts J. Biol. Chem., April 9, 1999; 274(15): 10609 - 10617. [Abstract] [Full Text] [PDF]

				C. Ohlsson, B.-A. Bengtsson, O. G. P. Isaksson, T. T. Andreassen, and M. C. Slootweg Growth Hormone and Bone Endocr. Rev., February 1, 1998; 19(1): 55 - 79. [Abstract] [Full Text]

				Y. Umayahara, C. Ji, M. Centrella, P. Rotwein, and T. L. McCarthy CCAAT/Enhancer-binding Protein delta  Activates Insulin-like Growth Factor-I Gene Transcription in Osteoblasts. IDENTIFICATION OF A NOVEL CYCLIC AMP SIGNALING PATHWAY IN BONE J. Biol. Chem., December 12, 1997; 272(50): 31793 - 31800. [Abstract] [Full Text] [PDF]

				N. Franchimont, V. Gangji, D. Durant, and E. Canalis Interleukin-6 with Its Soluble Receptor Enhances the Expression of Insulin-Like Growth Factor-I in Osteoblasts Endocrinology, December 1, 1997; 138(12): 5248 - 5255. [Abstract] [Full Text] [PDF]

				X. Wang, Y. Yang, and M. L. Adamo Characterization of the Rat Insulin-Like Growth Factor I Gene Promoters and Identification of a Minimal Exon 2 Promoter Endocrinology, April 1, 1997; 138(4): 1528 - 1536. [Abstract] [Full Text] [PDF]

				M. J. Thomas, Y. Umayahara, H. Shu, M. Centrella, P. Rotwein, and T. L. McCarthy Identification of the cAMP Response Element That Controls Transcriptional Activation of the Insulin-like Growth Factor-I Gene by Prostaglandin E2 in Osteoblasts J. Biol. Chem., September 6, 1996; 271(36): 21835 - 21841. [Abstract] [Full Text] [PDF]

				B. Gabbitas, J. M. Pash, A. M. Delany, and E. Canalis Cortisol Inhibits the Synthesis of Insulin-like Growth Factor-binding Protein-5 in Bone Cell Cultures by Transcriptional Mechanisms J. Biol. Chem., April 12, 1996; 271(15): 9033 - 9038. [Abstract] [Full Text] [PDF]

				A. M. Delany, J. J. Jeffrey, S. Rydziel, and E. Canalis Cortisol Increases Interstitial Collagenase Expression in Osteoblasts by Post-transcriptional Mechanisms J. Biol. Chem., November 3, 1995; 270(44): 26607 - 26612. [Abstract] [Full Text] [PDF]

				J. Billiard, Y. Umayahara, K. Wiren, M. Centrella, T. L. McCarthy, and P. Rotwein Regulated Nuclear-Cytoplasmic Localization of CCAAT/ Enhancer-binding Protein delta in Osteoblasts J. Biol. Chem., April 27, 2001; 276(18): 15354 - 15361. [Abstract] [Full Text] [PDF]