Journal of Clinical Endocrinology & Metabolism, Vol 79, 1871-1876, Copyright © 1994 by Endocrine Society

ARTICLES

Differential cellular synthesis of insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 within human liver

E Arany, S Afford, AJ Strain, PJ Winwood, MJ Arthur and DJ Hill
Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph's Health Center, London, Ontario, Canada.

The two major insulin-like growth factor-binding protein (IGFBP) species in the human circulation, IGFBP-1 and IGFBP-3, are synthesized in large amounts by liver. To determine which hepatic cell populations in human liver were responsible for the synthesis and release of these IGFBPs, we 1) performed in situ hybridization with specific complementary RNA (RNA) probes for human IGFBP-1 or-3 or performed immunohistochemical analysis to reveal the sites of messenger RNA (mRNA) presence and peptide translation, respectively, in sections of normal liver derived from organ donors; and 2) examined the release of IGFBP species by Western ligand and immunoblots of medium conditioned by isolated cultures of hepatocytes, lipocytes, and Kupffer cells. In situ hybridization showed that IGFBP-1 mRNA was distributed widely among the parenchymal cell population, which also showed immunohistochemical staining for IGFBP-1 peptide. Conversely, IGFBP-3 mRNA and immunoreactive peptide were mainly localized to Kupffer cells, which were positively identified by immunoreactivity with antiserum against the glycoprotein marker, CD68. Isolated hepatocytes released two species of IGFBP of 28 and 30-32 kilodaltons, which were recognized immunologically as IGFBP-1. Isolated Kupffer cells released only a 43- to 46-kilodalton IGFBP immunologically recognized as IGFBP-3. Lipocyte cultures released no detectable IGFBP species. The results suggest that IGFBP-1 and IGFBP-3 are derived from separate cell populations in human liver.

This article has been cited by other articles:

				P. F. Collett-Solberg, M. Misra, and on behalf of the Drug and Therapeutics Committee o The Role of Recombinant Human Insulin-Like Growth Factor-I in Treating Children with Short Stature J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 10 - 18. [Abstract] [Full Text] [PDF]

				X. F. Lu, X. G. Jiang, Y. B. Lu, J. H. Bai, and Z. B. Mao Characterization of a Novel Positive Transcription Regulatory Element That Differentially Regulates the Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Gene in Senescent Cells J. Biol. Chem., June 17, 2005; 280(24): 22606 - 22615. [Abstract] [Full Text] [PDF]

				R. P. Peeters, A. W. van den Beld, H. van Toor, A. G. Uitterlinden, J. A. M. J. L. Janssen, S. W. J. Lamberts, and T. J. Visser A Polymorphism in Type I Deiodinase Is Associated with Circulating Free Insulin-Like Growth Factor I Levels and Body Composition in Humans J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 256 - 263. [Abstract] [Full Text] [PDF]

				H. Huynh, P. K. H. Chow, L. L. P. Ooi, and K.-C. Soo A Possible Role for Insulin-like Growth Factor-binding Protein-3 Autocrine/Paracrine Loops in Controlling Hepatocellular Carcinoma Cell Proliferation Cell Growth Differ., March 1, 2002; 13(3): 115 - 122. [Abstract] [Full Text] [PDF]

				F. De Benedetti, C. Meazza, M. Oliveri, P. Pignatti, M. Vivarelli, T. Alonzi, E. Fattori, S. Garrone, A. Barreca, and A. Martini Effect of IL-6 on IGF Binding Protein-3: A Study in IL-6 Transgenic Mice and in Patients with Systemic Juvenile Idiopathic Arthritis Endocrinology, November 1, 2001; 142(11): 4818 - 4826. [Abstract] [Full Text] [PDF]

				J-G Scharf, F Dombrowski, and G Ramadori The IGF axis and hepatocarcinogenesis Mol. Pathol., June 1, 2001; 54(3): 138 - 144. [Abstract] [Full Text]

				E. M. Zimmermann, L. Li, E. C. Hoyt, J. B. Pucilowska, S. Lichtman, and P. K. Lund Cell-specific localization of insulin-like growth factor binding protein mRNAs in rat liver Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G447 - G457. [Abstract] [Full Text] [PDF]

				R. I. G. Holt, J. S. Jones, A. J. Baker, C. R. Buchanan, and J. P. Miell The Effect of Short Stature, Portal Hypertension, and Cholestasis on Growth Hormone Resistance in Children with Liver Disease J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3277 - 3282. [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]

				R. A. Hill and J. M. Pell Regulation of Insulin-Like Growth Factor I (IGF-I) Bioactivity in Vivo: Further Characterization of an IGF-I-Enhancing Antibody Endocrinology, March 1, 1998; 139(3): 1278 - 1287. [Abstract] [Full Text] [PDF]

				S. Skrtic, V. Wallenius, S. Ekberg, A. Brenzel, A. M. Gressner, and J.-O. Jansson Insulin-Like Growth Factors Stimulate Expression of Hepatocyte Growth Factor But Not Transforming Growth Factor {beta}1 in Cultured Hepatic Stellate Cells Endocrinology, November 1, 1997; 138(11): 4683 - 4689. [Abstract] [Full Text] [PDF]