Submitted on January 22, 2007
Accepted on April 18, 2007
Growth Hormone Regulation of Metabolic Gene Expression in Muscle: A Microarray Study in Hypopituitary Men
Klara Sjögren1, Kin-Chuen Leung2, Warren Kaplan3, Margaret Gardiner-Garden4, James Gibney5, and Ken KY Ho6*
1 Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Dpeartment of Internal Medicine, Sahlgrenska Academy at Goteborg University, Goteborg, Sweden
2 Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
3 Peter Wills Bioinformatics Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
4 Cancer Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
5 Pituitary Research Unit, Garvan Institute of Medical Research, Australia
6 Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Department of Endocrinology, St Vincents Hospital, Sydney, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: k.ho{at}garvan.unsw.edu.au.
Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic process in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes regulating substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after two weeks of GH treatment (0.5mg/day). Transcript profiles of four subjects were analysed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I), procollagens I and III were measured by RIA. GH increased serum IGF-I, procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.
