This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Ye, P. Articles by D’Ercole, A. J. Search for Related Content PubMed PubMed Citation Articles by Ye, P. Articles by D’Ercole, A. J.

Regulation of Insulin-Like Growth Factor I (IGF-I) Gene Expression in Brain of Transgenic Mice Expressing an IGF-I-Luciferase Fusion Gene¹

Department of Pediatrics, University of North Carolina at Chapel Hill (P.Y., T.B., H.A., A.J.D’E.), Chapel Hill, North Carolina 27599; and Departments of Biochemistry and Medicine, Washington University School of Medicine (Y.U., D.R., P.R.), St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Dr. A. J. D’Ercole, Department of Pediatrics, CB 7220, 509 Burnett-Womack, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220.

Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5–4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77–388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.

This article has been cited by other articles:

				S. Eleswarapu, Z. Gu, and H. Jiang Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites Endocrinology, May 1, 2008; 149(5): 2230 - 2240. [Abstract] [Full Text] [PDF]

				S. S. Daftary and A. C. Gore IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function Experimental Biology and Medicine, May 1, 2005; 230(5): 292 - 306. [Abstract] [Full Text] [PDF]

				Y. Wang and H. Jiang Identification of a Distal STAT5-binding DNA Region That May Mediate Growth Hormone Regulation of Insulin-like Growth Factor-I Gene Expression J. Biol. Chem., March 25, 2005; 280(12): 10955 - 10963. [Abstract] [Full Text] [PDF]

				J. Woelfle, J. Billiard, and P. Rotwein Acute Control of Insulin-like Growth Factor-I Gene Transcription by Growth Hormone through Stat5b J. Biol. Chem., June 13, 2003; 278(25): 22696 - 22702. [Abstract] [Full Text] [PDF]

				N. D. Aberg, B. Carlsson, L. Rosengren, J. Oscarsson, O. G. P. Isaksson, L. Ronnback, and P. S. Eriksson Growth Hormone Increases Connexin-43 Expression in the Cerebral Cortex and Hypothalamus Endocrinology, October 1, 2000; 141(10): 3879 - 3886. [Abstract] [Full Text] [PDF]

				C. Benbassat, L. N. N. Shoba, M. Newman, M. L. Adamo, S. J. Frank, and W. L. Lowe Jr. Growth Hormone-Mediated Regulation of Insulin-Like Growth Factor I Promoter Activity in C6 Glioma Cells Endocrinology, July 1, 1999; 140(7): 3073 - 3081. [Abstract] [Full Text]

				E. E. Muller, V. Locatelli, and D. Cocchi Neuroendocrine Control of Growth Hormone Secretion Physiol Rev, April 1, 1999; 79(2): 511 - 607. [Abstract] [Full Text] [PDF]