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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on November 11, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/glp172
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

The Effects of Growth hormone (GH) Treatment on GH and Insulin/IGF-1 Signaling in Long-Lived Ames Dwarf Mice

Michal M. Masternak1, Jacob A. Panici1, Feiya Wang1, Zhihui Wang1,2 and Adam Spong1

1 Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield
2 Division of Diabetes, Endocrinology, and Metabolism, School of Medicine, Vanderbilt University, Nashville, Tennessee

Address correspondence to Michal M. Masternak, PhD, Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, 801 N. Rutledge, Room 4389, PO Box 19628, Springfield, IL 62794-9628. Email: mmasternak{at}siumed.edu


  Abstract

The disruption of the growth hormone (GH) axis in mice promotes insulin sensitivity and is strongly correlated with extended longevity. Ames dwarf (Prop1df, df/df) mice are GH, prolactin (PRL), and thyrotropin (TSH) deficient and live approximately 50% longer than their normal siblings. To investigate the effects of GH on insulin and GH signaling pathways, we subjected these dwarf mice to twice-daily GH injections (6 µg/g/d) starting at the age of 2 weeks and continuing for 6 weeks. This produced the expected activation of the GH signaling pathway and stimulated somatic growth of the Ames dwarf mice. However, concomitantly with increased growth and increased production of insulinlike growth factor-1, the GH treatment strongly inhibited the insulin signaling pathway by decreasing insulin sensitivity of the dwarf mice. This suggests that improving growth of these animals may negatively affect both their healthspan and longevity by causing insulin resistance.

Keywords Ames dwarf; Aging; Insulin; Growth hormone

Received: August 28, 2009; Accepted: October 11, 2009

Decision Editor: Huber R. Warner, PhD


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