Endocrinology, Vol 137, 55-64, Copyright © 1996 by Endocrine Society

ARTICLES

Acute nuclear actions of growth hormone (GH): cycloheximide inhibits inducible activator protein-1 activity, but does not block GH-regulated signal transducer and activator of transcription activation or gene expression

AM Gronowski, C Le Stunff and P Rotwein
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The mechanisms by which GH regulates gene expression to stimulate somatic growth and alter intermediary metabolism are unknown. We have shown previously that in vivo GH administration rapidly modifies the tyrosine phosphorylation of multiple hepatic nuclear proteins, including the inducible transcription factors, Stat1, Stat3, and (in this report) Stat5, and have found that hormone treatment also rapidly alters gene transcription in the liver. In this study, we have used the protein synthesis inhibitor, cycloheximide (CHX), to investigate which of the acute actions of GH are primary hormonal responses and which require concurrent protein synthesis. We found that many of the early changes in nuclear protein tyrosine phosphorylation and in nuclear protein-DNA binding after GH are not blunted by CHX. The activation of insulin-like growth factor I and Spi 2.1 gene expression and the inhibition of albumin transcription also are not blocked by CHX, suggesting that these effects are primary consequences of GH-activated signal transduction pathways. By contrast, CHX completely inhibits the induction of activator protein-1 DNA-binding activity by GH, indicating that this action is secondary to the stimulation of Fos and/or Jun protein biosynthesis. Our results support the idea that multiple primary and secondary signaling pathways contribute to the pleiotropic effects of GH on gene expression and provide a framework for delineating the mechanisms controlling the acute actions of GH.

This article has been cited by other articles:

				A. Hosui and L. Hennighausen Genomic dissection of the cytokine-controlled STAT5 signaling network in liver Physiol Genomics, July 9, 2008; 34(2): 135 - 143. [Abstract] [Full Text] [PDF]

				T. X. Cui, R. Kwok, and J. Schwartz Cooperative regulation of endogenous cAMP-response element binding protein and CCAAT/enhancer-binding protein in GH-stimulated c-fos expression J. Endocrinol., January 1, 2008; 196(1): 89 - 100. [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 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]

				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]

				P. L. Bergad, S. J. Schwarzenberg, J. T. Humbert, M. Morrison, S. Amarasinghe, H. C. Towle, and S. A. Berry Inhibition of growth hormone action in models of inflammation Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1906 - C1917. [Abstract] [Full Text] [PDF]

				H. K. Choi and D. J. Waxman Plasma Growth Hormone Pulse Activation of Hepatic JAK-STAT5 Signaling: Developmental Regulation and Role in Male-Specific Liver Gene Expression Endocrinology, September 1, 2000; 141(9): 3245 - 3255. [Abstract] [Full Text] [PDF]

				P. L. Bergad, H. C. Towle, and S. A. Berry Yin-yang 1 and Glucocorticoid Receptor Participate in the Stat5-mediated Growth Hormone Response of the Serine Protease Inhibitor 2.1 Gene J. Biol. Chem., March 10, 2000; 275(11): 8114 - 8120. [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]

				G. T. Ooi, K. R. Hurst, M. N. Poy, M. M. Rechler, and Y. R. Boisclair Binding of STAT5a and STAT5b to a Single Element Resembling a {gamma}-Interferon-Activated Sequence Mediates the Growth Hormone Induction of the Mouse Acid-Labile Subunit Promoter in Liver Cells Mol. Endocrinol., May 1, 1998; 12(5): 675 - 687. [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]

				S. J. Ruff, K. Chen, and S. Cohen Peroxovanadate Induces Tyrosine Phosphorylation of Multiple Signaling Proteins in Mouse Liver and Kidney J. Biol. Chem., January 10, 1997; 272(2): 1263 - 1267. [Abstract] [Full Text] [PDF]