Endocrinology, Vol 136, 4741-4748, Copyright © 1995 by Endocrine Society

ARTICLES

Rapid changes in gene expression after in vivo growth hormone treatment

AM Gronowski and P Rotwein
Department of Biochemistry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

GH exerts long-lasting effects on somatic growth via changes in gene expression and protein biosynthesis that represent the culmination of signal transduction pathways initiated at the cell surface. Recent studies have demonstrated that ligand-induced activation of the GH receptor leads to the phosphorylation of multiple intracellular proteins, including latent cytoplasmic transcription factors, Stats 1 and 3. GH treatment also has been found to induce the expression of several genes in both in vitro and in vivo systems, and we have shown that GH rapidly activates insulin-like growth factor I (IGF-I) gene transcription in hypophysectomized rats. In this study, using the GH- deficient, hypophysectomized rat as a model, we have examined the earliest changes in gene expression that follow a single systemic injection of GH. We find that GH induces nascent nuclear IGF-I transcripts within 15 min of hormone treatment, a time course that parallels the GH-regulated appearance of nuclear c-fos messenger RNA (mRNA). By contrast, nuclear transcripts for c-jun did not increase in abundance until after 30 min after hormone injection, and the peak rise in c-jun mRNA was severalfold less than for c-fos or IGF-I. GH treatment also led to the acute inhibition of IGF binding protein-1 (IGFBP-1) and albumin gene expression. Nuclear IGFBP-1 mRNA levels declined to 60% of baseline at 30 min and to 30% at 60 min, in agreement with previous studies showing a reduction in IGFBP-1 transcription after GH. Nascent nuclear albumin transcripts also decreased in abundance after GH treatment to levels that were less than 20% of basal values at 30 and 60 min. Our results show that GH can acutely activate and inhibit gene expression in the liver. It is likely that these diverse effects of GH are mediated by multiple signal transduction pathways.

This article has been cited by other articles:

				V. Wauthier and D. J. Waxman Sex-Specific Early Growth Hormone Response Genes in Rat Liver Mol. Endocrinol., August 1, 2008; 22(8): 1962 - 1974. [Abstract] [Full Text] [PDF]

				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]

				M. Ono, D. J. Chia, R. Merino-Martinez, A. Flores-Morales, T. G. Unterman, and P. Rotwein Signal Transducer and Activator of Transcription (Stat) 5b-Mediated Inhibition of Insulin-Like Growth Factor Binding Protein-1 Gene Transcription: A Mechanism for Repression of Gene Expression by Growth Hormone Mol. Endocrinol., June 1, 2007; 21(6): 1443 - 1457. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				S. Fruchtman, J. G. Simmons, C. Z. Michaylira, M. E. Miller, C. J. Greenhalgh, D. M. Ney, and P. K. Lund Suppressor of cytokine signaling-2 modulates the fibrogenic actions of GH and IGF-I in intestinal mesenchymal cells Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G342 - G350. [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]

				S Eleswarapu and H Jiang Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver J. Endocrinol., January 1, 2005; 184(1): 95 - 105. [Abstract] [Full Text] [PDF]

				J. Woelfle and P. Rotwein In vivo regulation of growth hormone-stimulated gene transcription by STAT5b Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E393 - E401. [Abstract] [Full Text] [PDF]

				E. M. Dahly, M. E. Miller, P. K. Lund, and D. M. Ney Postreceptor Resistance to Exogenous Growth Hormone Exists in the Jejunal Mucosa of Parenterally Fed Rats J. Nutr., March 1, 2004; 134(3): 530 - 537. [Abstract] [Full Text] [PDF]

				H. Yoshizato, M. Tanaka, N. Nakai, N. Nakao, and K. Nakashima Growth Hormone (GH)-Stimulated Insulin-Like Growth Factor I Gene Expression Is Mediated by a Tyrosine Phosphorylation Pathway Depending on C-Terminal Region of Human GH Receptor in Human GH Receptor-Expressing Ba/F3 Cells Endocrinology, January 1, 2004; 145(1): 214 - 220. [Abstract] [Full Text] [PDF]

				J. Woelfle, D. J. Chia, and P. Rotwein Mechanisms of Growth Hormone (GH) Action: IDENTIFICATION OF CONSERVED Stat5 BINDING SITES THAT MEDIATE GH-INDUCED INSULIN-LIKE GROWTH FACTOR-I GENE ACTIVATION J. Biol. Chem., December 19, 2003; 278(51): 51261 - 51266. [Abstract] [Full Text] [PDF]

				R. P. Radcliff, B. L. McCormack, B. A. Crooker, and M. C. Lucy Growth Hormone (GH) Binding and Expression of GH Receptor 1A mRNA in Hepatic Tissue of Periparturient Dairy Cows J Dairy Sci, December 1, 2003; 86(12): 3933 - 3940. [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]

				L. N. N. Shoba, M. Newman, W. Liu, and W. L. Lowe Jr. LY 294002, an Inhibitor of Phosphatidylinositol 3-Kinase, Inhibits GH-Mediated Expression of the IGF-I Gene in Rat Hepatocytes Endocrinology, September 1, 2001; 142(9): 3980 - 3986. [Abstract] [Full Text] [PDF]

				B. Contreras and F. Talamantes Growth Hormone (GH) and 17{beta}-Estradiol Regulation of the Expression of Mouse GH Receptor and GH-Binding Protein in Cultured Mouse Hepatocytes Endocrinology, October 1, 1999; 140(10): 4725 - 4731. [Abstract] [Full Text]

				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]

				A. Barreca, M. Bozzola, A. Cesarone, P. H. Steenbergh, P. E. Holthuizen, F. Severi, G. Giordano, and F. Minuto Short Stature Associated with High Circulating Insulin-Like Growth Factor (IGF)-Binding Protein-1 and Low Circulating IGF-II: Effect of Growth Hormone Therapy J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3534 - 3541. [Abstract] [Full Text]

				C. Le Stunff and P. Rotwein Growth Hormone Stimulates Interferon Regulatory Factor-1 Gene Expression in the Liver Endocrinology, March 1, 1998; 139(3): 859 - 866. [Abstract] [Full Text] [PDF]

				G. T. Ooi, F. J. Cohen, L. Y.-H. Tseng, M. M. Rechler, and Y. R. Boisclair Growth Hormone Stimulates Transcription of the Gene Encoding the Acid-Labile Subunit (ALS) of the Circulating Insulin-Like Growth Factor-Binding Protein Complex and ALS Promoter Activity in Rat Liver Mol. Endocrinol., June 1, 1997; 11(7): 997 - 1007. [Abstract] [Full Text]