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This version published online on May 30, 2003
Endocrinology, doi:10.1210/en.2003-0374
A more recent version of this article appeared on September 1, 2003
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Submitted on March 26, 2003
Accepted on May 19, 2003

Deletion, but not Antagonism, of the Mouse Growth Hormone Receptor Results in Severely Decreased Body Weights, Insulin and IGF-I Levels and Increased Lifespan

KAREN T. COSCHIGANO1*, AMY N. HOLLAND1, MARKUS E. RIDERS1, EDWARD O. LIST1, ALLAN FLYVBJERG1, and JOHN J. KOPCHICK1

1 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, OH 45701; and Medical Research Laboratories, Institute of Experimental Clinical Research (A.F.), Aarhus Kommunehospital, Aarhus, Denmark

* To whom correspondence should be addressed. E-mail: coschigk{at}ohio.edu.

Growth hormone (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 -/-). Herein, 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 while 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. Insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) levels were significantly reduced, but by different degrees, in both mouse lines, while IGFBP-1 and -4 levels were reduced and IGFBP-2 levels increased in GHR -/- mice but unaltered in GHA mice. Finally, lifespan 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.


Key words: growth hormone antagonist • growth hormone receptor knockout • dwarfism • lifespan • insulin







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