All ETDs from UAB

Advisory Committee Chair

Thomas L Clemens

Advisory Committee Members

Candece L Gladson

Stuart J Frank

Susan L Bellis

Marcas M Bamman

Document Type

Dissertation

Date of Award

2009

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the impact of selected genetic alterations in the GH-IGF-1 pathway on skeletal muscle development and function in mice. With the results from these studies, I demonstrate that GH mediates skeletal muscle development by enhancing myoblast fusion in an IGF-1 dependent manner. In addition, I also demonstrate that disruption of the GHR in skeletal muscle leads to alterations in global energy utilization and insulin resistance in an IGF-1 independent manner.

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