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


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


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.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.