This Article Full Text Full Text (PDF) 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, J.-L. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Liu, J.-L. Articles by LeRoith, D.

Mice Deficient in Liver Production of Insulin-Like Growth Factor I Display Sexual Dimorphism in Growth Hormone-Stimulated Postnatal Growth

Clinical Endocrinology Branch, NIDDK, National Institutes of Health, 10/8D12, 10 Center Drive, Bethesda, Maryland 20892-1758

Address all correspondence and requests for reprints to: Derek LeRoith, M.D., Ph.D., CEB/NIDDK, Building 10, Room 8D12, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1758. E-mail: Derek{at}helix.nih.gov

Insulin-like growth factor I (IGF-I) is essential for normal intrauterine and postnatal growth and development. Using the Cre/loxP-induced conditional knockout system, we have established a liver-specific IGF-I-deficient (LID) mouse model. Circulating IGF-I levels were decreased by approximately75% without any apparent effect on their growth and development. To determine the role of extra-hepatic IGF-I in GH-induced postnatal growth, we tested the effects of GH on growth rates in these mice. Female, but not male, LID mice displayed significantly accelerated growth rates in response to daily injections of GH for 5 weeks. The GH-induced peripubertal growth in female LID mice was not affected by ovariectomy, nor did castration change the growth pattern in male LID mice. Thus, factors other than gonadal steroids mediate this sexual dimorphism. We postulate that the sexual dimorphic response to GH observed in LID mice may be related to genetically programmed differences in GH secretion patterns.

This article has been cited by other articles:

				J. Mao, T. Yang, Z. Gu, W. C. Heird, M. J. Finegold, B. Lee, and S. J. Wakil aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues PNAS, October 13, 2009; 106(41): 17576 - 17581. [Abstract] [Full Text] [PDF]

				M. O. Thorner Statement by the Growth Hormone Research Society on the GH/IGF-I Axis in Extending Health Span J Gerontol A Biol Sci Med Sci, October 1, 2009; 64A(10): 1039 - 1044. [Abstract] [Full Text] [PDF]

				I. Ueki, S. L. Giesy, K. J. Harvatine, J. W. Kim, and Y. R. Boisclair The Acid-Labile Subunit Is Required for Full Effects of Exogenous Growth Hormone on Growth and Carbohydrate Metabolism Endocrinology, July 1, 2009; 150(7): 3145 - 3152. [Abstract] [Full Text] [PDF]

				A. P. R. Sutherland, H. Zhang, Y. Zhang, M. Michaud, Z. Xie, M.-E. Patti, M. J. Grusby, and W. J. Zhang Zinc Finger Protein Zbtb20 Is Essential for Postnatal Survival and Glucose Homeostasis Mol. Cell. Biol., May 15, 2009; 29(10): 2804 - 2815. [Abstract] [Full Text] [PDF]

				E. Stratikopoulos, M. Szabolcs, I. Dragatsis, A. Klinakis, and A. Efstratiadis The hormonal action of IGF1 in postnatal mouse growth PNAS, December 9, 2008; 105(49): 19378 - 19383. [Abstract] [Full Text] [PDF]

				K. E. Govoni, J. E. Wergedal, R. B. Chadwick, A. K. Srivastava, and S. Mohan Prepubertal OVX increases IGF-I expression and bone accretion in C57BL/6J mice Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1172 - E1180. [Abstract] [Full Text] [PDF]

				K. E. Govoni, J. E. Wergedal, L. Florin, P. Angel, D. J. Baylink, and S. Mohan Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion Endocrinology, December 1, 2007; 148(12): 5706 - 5715. [Abstract] [Full Text] [PDF]

				P. Klover and L. Hennighausen Postnatal Body Growth Is Dependent on the Transcription Factors Signal Transducers and Activators of Transcription 5a/b in Muscle: A Role for Autocrine/Paracrine Insulin-Like Growth Factor I Endocrinology, April 1, 2007; 148(4): 1489 - 1497. [Abstract] [Full Text] [PDF]

				J. E. Rowland, L. M. Kerr, M. White, P. G. Noakes, and M. J. Waters Heterozygote Effects in Mice with Partial Truncations in the Growth Hormone Receptor Cytoplasmic Domain: Assessment of Growth Parameters and Phenotype Endocrinology, December 1, 2005; 146(12): 5278 - 5286. [Abstract] [Full Text] [PDF]

				Z. Tang, R. Yu, Y. Lu, A. F. Parlow, and J.-L. Liu Age-dependent onset of liver-specific IGF-I gene deficiency and its persistence in old age: implications for postnatal growth and insulin resistance in LID mice Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E288 - E295. [Abstract] [Full Text] [PDF]

				S. S. Daftary and A. C. Gore IGF-1 in the Brain as a Regulator of Reproductive Neuroendocrine Function Experimental Biology and Medicine, May 1, 2005; 230(5): 292 - 306. [Abstract] [Full Text] [PDF]

				Z. D. Sharp and A. Bartke Evidence for Down-Regulation of Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR)-Dependent Translation Regulatory Signaling Pathways in Ames Dwarf Mice J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2005; 60(3): 293 - 300. [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]

				J. D. Veldhuis, S. M. Anderson, P. Kok, A. Iranmanesh, J. Frystyk, H. Orskov, and D. M. Keenan Estradiol Supplementation Modulates Growth Hormone (GH) Secretory-Burst Waveform and Recombinant Human Insulin-Like Growth Factor-I-Enforced Suppression of Endogenously Driven GH Release in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1312 - 1318. [Abstract] [Full Text] [PDF]

				C. Ibarra, M. Estrada, L. Carrasco, M. Chiong, J. L. Liberona, C. Cardenas, G. Diaz-Araya, E. Jaimovich, and S. Lavandero Insulin-like Growth Factor-1 Induces an Inositol 1,4,5-Trisphosphate-dependent Increase in Nuclear and Cytosolic Calcium in Cultured Rat Cardiac Myocytes J. Biol. Chem., February 27, 2004; 279(9): 7554 - 7565. [Abstract] [Full Text] [PDF]

				N. R. Biermasz, A. M. Pereira, M. Frolich, J. A. Romijn, J. D. Veldhuis, and F. Roelfsema Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E25 - E30. [Abstract] [Full Text]

				W. E. Sonntag and M. M. Ramsey Of Worms, Flies, Dwarfs, and Things That Go Bump in the Night Sci. Aging Knowl. Environ., October 30, 2002; 2002(43): pe17 - 17. [Abstract] [Full Text]

				D. C. O'Sullivan, T. A. M. Szestak, and J. M. Pell Regulation of IGF-I mRNA by GH: putative functions for class 1 and 2 message Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E251 - E258. [Abstract] [Full Text] [PDF]

				A. A. Butler and D. LeRoith Minireview: Tissue-Specific Versus Generalized Gene Targeting of the igf1 and igf1r Genes and Their Roles in Insulin-Like Growth Factor Physiology Endocrinology, May 1, 2001; 142(5): 1685 - 1688. [Abstract] [Full Text]