Regulation of insulin-like growth factor-I in skeletal muscle and muscle cells.
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are potent regulators of muscle mass. Transgenic mice that over-express these proteins exhibit dramatically enlarged skeletal muscles. In contrast, malnutrition, critical illness, sepsis, and aging are all associated with a dramatic reduction in muscle mass and function. The circulating concentration of IGF-I and the expression of IGF-I in skeletal muscle are also reduced during catabolic states. Consequently, GH has been used clinically to increase lean body mass in patients with muscle wasting. Likewise, delivery of IGF-I specifically into muscle has been proposed as a genetic therapy for muscle disorders. A better understanding of the regulation of IGF-I expression in skeletal muscle and muscle cells is therefore of importance. Yet, our knowledge in this area has been limited by a lack of GH responsive muscle cells. In addition the IGF-I gene spans over 90 kb of genomic DNA and it exhibits a very complex regulatory pattern. This review will summarize our knowledge of the control of muscle mass by GH, IGF-I, anabolic steroids, exercise and other growth enhancing hormones. We will also highlight recent advances in the regulation of IGF-I and signal transducers and activators of transcription (Stats) by GH. A special emphasis will be placed on the interaction of IGF-I and proinflammatory cytokines in skeletal muscle and muscle cells.
Frost
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Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University Hershey, PA 17033, USA. RFROST@PSU.EDU
Lang
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D045930:Anabolic Agents / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000502:physiology; D015444:Exercise; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology / Q000633:toxicity; D006133:Growth Substances / Q000502:physiology; D019382:Human Growth Hormone / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D007239:Infections / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D009748:Nutrition Disorders / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
D045930:Anabolic Agents; D016207:Cytokines; D005938:Glucocorticoids; D006133:Growth Substances; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin