title: Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men.
abstract: 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 processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and 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.
authors: Pituitary Research Unit, Garvan Institute of Medical Research, 384 Victoria St., Sydney, NSW 2010, Australia.
authors: Klara
authors: K
authors: Sjögren
authors: Kin-Chuen
authors: KC
authors: Leung
authors: Warren
authors: W
authors: Kaplan
authors: Margaret
authors: M
authors: Gardiner-Garden
authors: James
authors: J
authors: Gibney
authors: Ken K Y
authors: KK
authors: Ho
mesh_terms: D000328:Adult; D000368:Aged; D003094:Collagen / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects* / Q000235:genetics; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D003094:Collagen