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Deletion, But Not Antagonism, of the Mouse Growth Hormone Receptor Results in Severely Decreased Body Weights, Insulin, and Insulin-Like Growth Factor I Levels and Increased Life Span

Edison Biotechnology Institute (K.T.C., A.N.H., M.E.R., E.O.L., J.J.K.) and Department of Biomedical Sciences, College of Osteopathic Medicine (J.J.K.), Ohio University, Athens, Ohio 45701; and Medical Research Laboratories (A.F.), Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus, Denmark

Address all correspondence and requests for reprints to: Dr. Karen T. Coschigano, Edison Biotechnology Institute, Ohio University, 101 Konneker Research Laboratories, The Ridges, Athens, Ohio 45701. E-mail: coschigk{at}ohio.edu.

GH participates in growth, metabolism, and cellular differentiation. To study these roles, we previously generated two different dwarf mouse lines, one expressing a GH antagonist (GHA) and the other having a disrupted GH receptor and binding protein gene (GHR -/-). In this study we compared the two dwarf lines in the same genetic background (C57BL/6J). One of the most striking differences between the mouse lines was their weight gain profile after weaning. The weights of the GHA dwarfs gradually approached controls over time, but the weights of the GHR -/- dwarfs remained low throughout the analysis period. Additionally, fasting insulin and glucose levels were reduced in the GHR -/- mice but normal in the GHA mice. IGF-I and IGF binding protein 3 (IGFBP-3) levels were significantly reduced, but by different degrees, in both mouse lines, but IGFBP-1 and -4 levels were reduced and IGFBP-2 levels increased in GHR -/- mice but unaltered in GHA mice. Finally, life span was significantly extended for the GHR -/- mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes.

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