All ETDs from UAB

Advisory Committee Chair

Joseph L Messina

Advisory Committee Members

Marcas M Bamman

Jeffrey D Kerby

Stuart J Frank

Rakesh P Patel

Document Type

Dissertation

Date of Award

2012

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Growth hormone (GH) regulates body composition via stimulation of protein synthesis and catabolism of adipose tissue, generally promoting maintenance of lean body mass. Following severe injury, GH resistance contributes to muscle protein wasting, adversely impacting morbidity and mortality. In this dissertation research, we sought to determine the mechanisms of GH resistance following injury. To accomplish this, we evaluated GH signaling in a mouse model of severe injury. In the first section of this thesis, we demonstrate severe impairments in hepatic GH signaling occurring in association with an apparent, hemorrhage-dependent cleavage of the GH receptor (GHR). In the second section, we demonstrate the rapid development of cardiac GH resistance following injury. Finally, we detail the effects of injury on GH signaling in skeletal muscle and adipose tissue. Throughout these studies, the effects of fasting (alone or in combination with hemorrhage) on GH signaling were also investigated. The results of our studies suggest that 1) hepatic GH signaling is influenced by rapid alterations in the availability of functional GHR during stress, 2) fasting prevents cardiac GH resistance following injury, and 3) GH resistance is a common response to stress in multiple tissues.

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