HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 38, 35444-35449, September 21, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/38/35444    most recent M105418200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fournier, B. Articles by Matthias, P. Search for Related Content PubMed PubMed Citation Articles by Fournier, B. Articles by Matthias, P.

Estrogen Receptor (ER)-, but Not ER-, Mediates Regulation of the Insulin-like Growth Factor I Gene by Antiestrogens^*

Brigitte Fournier^§, Sabine Gutzwiller, Tanja Dittmar, Gabriele Matthias^¶, Paul Steenbergh, and Patrick Matthias^¶

From the  Arthritis & Bone Metabolism Therapeutic Area, Novartis Pharma Research, 4002 Basel, Switzerland,  Department of Physiological Chemistry, University Medical Center, Utrecht 3584, The Netherlands, and ^¶ Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland

The importance of insulin-like growth factor I (IGF-I) on maintenance of skeletal integrity has been widely recognized. Although osteoblasts secrete some IGF-I, the liver is the primary endocrine source for IGF-I. We have studied the regulation of the human IGF-I promoter in the hepatocyte cell line Hep3B, and we have shown that the IGF-I promoter, when co-transfected in Hep3B cells together with an estrogen receptor (ER)- expression vector, was transcriptionally regulated by raloxifene or raloxifene-like molecules but not by 17-estradiol and 4(OH)-tamoxifen. The induction mediated by raloxifene is antagonized by 17-estradiol and mediated selectively by ER-, but not by ER-. Transfer of IGF-I promoter sequences from 733 to 65 or from 375 to 65 to a minimal Fos promoter resulted in a comparable responsiveness to raloxifene. This region contains two CAAT/enhancer-binding protein sites and an activator protein 1 site, both of which have been shown to be involved in estrogen receptor-mediated transactivation. When the CAAT/enhancer-binding protein sites were mutated in a construct bearing the sequence from 375 to 65 in front of the minimal Fos promoter, raloxifene induction was reduced, whereas mutation of the other elements did not affect induction. In addition, using chimeric proteins, we delineated the domains of ER- that confer to ER- transactivation abilities on the IGF-I promoter that are not exhibited by ER-. These data shed new light on the mechanism of action of antiestrogens and might help explain, at least in part, the bone-protective effects observed for some antiestrogens in ovariectomized animals.

This article has been cited by other articles:

				R. Shao, E. Egecioglu, B. Weijdegard, J. J. Kopchick, J. Fernandez-Rodriguez, N. Andersson, and H. Billig Dynamic regulation of estrogen receptor-{alpha} isoform expression in the mouse fallopian tube: mechanistic insight into estrogen-dependent production and secretion of insulin-like growth factors Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1430 - E1442. [Abstract] [Full Text] [PDF]

				G. Pandini, M. Genua, F. Frasca, S. Squatrito, R. Vigneri, and A. Belfiore 17{beta}-Estradiol Up-regulates the Insulin-like Growth Factor Receptor through a Nongenotropic Pathway in Prostate Cancer Cells Cancer Res., September 15, 2007; 67(18): 8932 - 8941. [Abstract] [Full Text] [PDF]

				L. K. Saxon, A. G. Robling, A. B. Castillo, S. Mohan, and C. H. Turner The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor-beta Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E484 - E491. [Abstract] [Full Text] [PDF]

				J. J. Christiansen, S. Fisker, C. H. Gravholt, P. Bennett, B. Svenstrup, M. Andersen, U. Feldt-Rasmussen, J. S. Christiansen, and J. O. L. Jorgensen Discontinuation of estrogen replacement therapy in GH-treated hypopituitary women alters androgen status and IGF-I Eur. J. Endocrinol., May 1, 2005; 152(5): 719 - 726. [Abstract] [Full Text] [PDF]

				R. P A Rooman, L. O. De Beeck, M. Martin, J. van Doorn, S. Mohan, and M. V L Du Caju Ethinylestradiol and testosterone have divergent effects on circulating IGF system components in adolescents with constitutional tall stature Eur. J. Endocrinol., April 1, 2005; 152(4): 597 - 604. [Abstract] [Full Text] [PDF]

				D. A. M. Salih, S. Mohan, Y. Kasukawa, G. Tripathi, F. A. Lovett, N. F. Anderson, E. J. Carter, J. E. Wergedal, D. J. Baylink, and J. M. Pell Insulin-Like Growth Factor-Binding Protein-5 Induces a Gender-Related Decrease in Bone Mineral Density in Transgenic Mice Endocrinology, February 1, 2005; 146(2): 931 - 940. [Abstract] [Full Text] [PDF]

				G. M. Leong, S. Moverare, J. Brce, N. Doyle, K. Sjogren, K. Dahlman-Wright, J.-A. Gustafsson, K. K. Y. Ho, C. Ohlsson, and K.-C. Leung Estrogen Up-Regulates Hepatic Expression of Suppressors of Cytokine Signaling-2 and -3 in Vivo and in Vitro Endocrinology, December 1, 2004; 145(12): 5525 - 5531. [Abstract] [Full Text] [PDF]

				V. Viereck, C. Grundker, S. Blaschke, B. Niederkleine, H. Siggelkow, K.-H. Frosch, D. Raddatz, G. Emons, and L. C. Hofbauer Raloxifene Concurrently Stimulates Osteoprotegerin and Inhibits Interleukin-6 Production by Human Trabecular Osteoblasts J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4206 - 4213. [Abstract] [Full Text] [PDF]