| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Growth and Development Section, Molecular and Cellular
Endocrinology Branch, National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health (G.T.O., F.J.C.,
L.Y.-H.T., M.M.R.), Bethesda, Maryland 20892,
Department of
Animal Sciences, Cornell University (Y.R.B.), Ithaca, New York
14853
The growth-promoting activity of GH, the principal hormonal determinant of body size, is mediated by insulin-like growth factor I (IGF-I). Most of the IGF-I in plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). The 150-kDa complex serves as a reservoir of IGF-I and determines its bioavailability to the tissues. Formation of the 150-kDa complex depends upon the synthesis of ALS, which is synthesized primarily in liver and is regulated by GH. The present study demonstrates that GH stimulates ALS gene transcription in rat liver and ALS promoter activity in a rat hepatoma cell line. ALS messenger RNA (mRNA) and ALS nuclear transcripts were decreased to similar extents in the livers of GH-deficient hypophysectomized rats. GH increased hepatic ALS mRNA within 3–4 h to about 65% of the levels seen in sham-operated control rats. To confirm that GH stimulated ALS gene transcription, we transiently transfected an ALS promoter-luciferase reporter gene construct into H4-II-E rat hepatoma cells and primary rat hepatocytes. Recombinant human GH (hGH) stimulated promoter activity about 3-fold. In contrast, basal promoter activity was lower, and GH stimulation was absent when the ALS reporter construct was transfected into GH-responsive 3T3-F442A mouse preadipocyte fibroblasts. GH stimulation of ALS promoter activity in H4-II-E cells was mediated by functional GH receptors; nonprimate (rat and bovine) GH gave identical stimulation to hGH, and stimulation by hGH occurred at physiological concentrations. Reverse transcriptase-PCR analysis indicated that GH receptor mRNA was present in H4-II-E cells at approximately 40% of the level seen in rat liver. GH also induced the expression of the endogenous c-fos gene, indicating that the signaling pathway necessary for the activation of gene expression by GH was intact in H4-II-E cells. Thus, H4-II-E cells are a GH-responsive liver cell line that should provide a useful system in which to study the molecular mechanism of transcriptional regulation by GH of ALS and other hepatic genes.
This article has been cited by other articles:
 |
|
 |
|
  J. W Kim, R. P Rhoads, N. Segoale, N. B Kristensen, D. E Bauman, and Y. R Boisclair Isolation of the cDNA encoding the acid labile subunit (ALS) of the 150 kDa IGF-binding protein complex in cattle and ALS regulation during the transition from pregnancy to lactation. J. Endocrinol., June 1, 2006; 189(3): 583 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Huo, R. C. McEachin, T. X. Cui, N. K. Duggal, T. Hai, D. J. States, and J. Schwartz Profiles of Growth Hormone (GH)-regulated Genes Reveal Time-dependent Responses and Identify a Mechanism for Regulation of Activating Transcription Factor 3 By GH J. Biol. Chem., February 17, 2006; 281(7): 4132 - 4141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Chia, M. Ono, J. Woelfle, M. Schlesinger-Massart, H. Jiang, and P. Rotwein Characterization of Distinct Stat5b Binding Sites That Mediate Growth Hormone-stimulated IGF-I Gene Transcription J. Biol. Chem., February 10, 2006; 281(6): 3190 - 3197. [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]
|
|
|
|
 |
|
 D. Mesotten, P. J. Wouters, R. P. Peeters, K. V. Hardman, J. M. Holly, R. C. Baxter, and G. Van den Berghe Regulation of the Somatotropic Axis by Intensive Insulin Therapy during Protracted Critical Illness J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3105 - 3113. [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]
|
|
|
|
 |
|
 H. M. Domene, S. V. Bengolea, A. S. Martinez, M. G. Ropelato, P. Pennisi, P. Scaglia, J. J. Heinrich, and H. G. Jasper Deficiency of the Circulating Insulin-like Growth Factor System Associated with Inactivation of the Acid-Labile Subunit Gene N. Engl. J. Med., February 5, 2004; 350(6): 570 - 577. [Full Text] [PDF]
|
|
|
|
|
|
W. H. Daughaday Free Insulin-Like Growth Factor (IGF) in Disorders of IGF Binding Protein 3 Complex Formation J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
 |
|
 S.-E. Kong, R. C. Baxter, and P. J. D. Delhanty Age-Dependent Regulation of the Acid-Labile Subunit in Response to Fasting-Refeeding in Rats Endocrinology, December 1, 2002; 143(12): 4505 - 4512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cisternino, M. Draghi, S. Lauriola, D. Scarcella, S. Bernasconi, L. Cavallo, F. De Luca, A. Lomeo, and L. Tato The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor-Binding Protein Complex in Girls with Central Precocious Puberty before and during Gonadotropin-Releasing Hormone Analog Therapy J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4629 - 4633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-E. Kong, S. M. Firth, R. C. Baxter, and P. J. D. Delhanty Regulation of the acid-labile subunit in sustained endotoxemia Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E692 - E701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. O'Brien, J. J. O'Shea, and C. Carter-Su SH2-B Family Members Differentially Regulate JAK Family Tyrosine Kinases J. Biol. Chem., March 1, 2002; 277(10): 8673 - 8681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Lang, G. J. Nystrom, and R. A. Frost Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R207 - R215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Silha, Y. Gui, T. Modric, A. Suwanichkul, S. K. Durham, D. R. Powell, and L. J. Murphy Overexpression of the Acid-Labile Subunit of the IGF Ternary Complex in Transgenic Mice Endocrinology, October 1, 2001; 142(10): 4305 - 4313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Davey, T. Xie, M. J. McLachlan, R. J. Wilkins, D. J. Waxman, and D. R. Grattan STAT5b Is Required for GH-Induced Liver Igf-I Gene Expression Endocrinology, September 1, 2001; 142(9): 3836 - 3841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Arosio, S. Garrone, P. Bruzzi, G. Faglia, F. Minuto, and A. Barreca Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3 J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1091 - 1098. [Abstract] [Full Text]
|
|
|
|
|
|
C. H. Lang, X. Liu, G. J. Nystrom, and R. A. Frost Acute response of IGF-I and IGF binding proteins induced by thermal injury Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E1087 - E1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Rhoads, P. L. Greenwood, A. W. Bell, and Y. R. Boisclair Organization and Regulation of the Gene Encoding the Sheep Acid-Labile Subunit of the 150-Kilodalton Insulin-Like Growth Factor-Binding Protein Complex Endocrinology, April 1, 2000; 141(4): 1425 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. R. Boisclair, J. Wang, J. Shi, K. R. Hurst, and G. T. Ooi Role of the Suppressor of Cytokine Signaling-3 in Mediating the Inhibitory Effects of Interleukin-1beta on the Growth Hormone-dependent Transcription of the Acid-labile Subunit Gene in Liver Cells J. Biol. Chem., February 11, 2000; 275(6): 3841 - 3847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Suwanichkul, Y. R. Boisclair, R. C. Olney, S. K. Durham, and D. R. Powell Conservation of a Growth Hormone-Responsive Promoter Element in the Human and Mouse Acid-Labile Subunit Genes Endocrinology, February 1, 2000; 141(2): 833 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ji, R. Guan, S. J. Frank, and J. L. Messina Insulin Inhibits Growth Hormone Signaling via the Growth Hormone Receptor/JAK2/STAT5B Pathway J. Biol. Chem., May 7, 1999; 274(19): 13434 - 13442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kanzaki and P. L. Morris Growth Hormone Regulates Steroidogenic Acute Regulatory Protein Expression and Steroidogenesis in Leydig Cell Progenitors Endocrinology, April 1, 1999; 140(4): 1681 - 1686. [Abstract] [Full Text]
|
|
|
|
|
|
H. Olivecrona, A. Hilding, C. Ekström, H. Barle, B. Nyberg, C. Möller, P. J. Delhanty, R. C. Baxter, B. Angelin, T. J. Ekström, et al. Acute and Short-Term Effects of Growth Hormone on Insulin-Like Growth Factors and Their Binding Proteins: Serum Levels and Hepatic Messenger Ribonucleic Acid Responses in Humans J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 553 - 560. [Abstract] [Full Text]
|
|
|
|
|
|
A. Juul, S. Møller, E. Mosfeldt-Laursen, M. H. Rasmussen, T. Scheike, S. A. Pedersen, K. W. Kastrup, H. Yu, J. Mistry, S. Rasmussen, et al. The Acid-Labile Subunit of Human Ternary Insulin-Like Growth Factor Binding Protein Complex in Serum: Hepatosplanchnic Release, Diurnal Variation, Circulating Concentrations in Healthy Subjects, and Diagnostic Use in Patients with Growth Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4408 - 4415. [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]
|
|
|
|
 |
|
 I. Ueki, G. T. Ooi, M. L. Tremblay, K. R. Hurst, L. A. Bach, and Y. R. Boisclair Inactivation of the acid labile subunit gene in mice results in mild retardation of postnatal growth despite profound disruptions in the circulating insulin-like growth factor system PNAS, June 6, 2000; 97(12): 6868 - 6873. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
