The Discovery of a Novel Growth Hormone Receptor and the Nutritional Regulation of the Growth Related Actions of Growth Hormone

• Main Author: Walock, Chad Napoleon
• Format: Others
• Published: North Dakota State University 2018
• Online Access: https://hdl.handle.net/10365/27453

The growth hormone (GH) family peptides such as GH, prolactin (PRL), and somatolactin (SL) regulate a wide array of physiological actions including but not limited to growth, metabolism, osmoregulation, and lipolysis. These actions are regulated by many factors both internal and external. I used rainbow trout (Oncorhynchus mykiss) as a model organism to study the effects of GH-family peptides, nutritional state, and serum on insulin-like growth factor (IGF) and growth hormone receptor (GHR) expression. Gene sequencing and phylogenic analysis was applied to characterize a novel GHR. Real-time quantitative-PCR was used to determine IGF and GHR expression levels in liver, muscle, and adipose tissue. Western blotting and pharmacological inhibitors were used to determine signaling pathways. A novel GHR was characterized and determined to be a type 1 GHR with a diverse distribution. It was found to have many features conserved in other GHRs including binding regions, a Y/FGEFS motif, cysteine residues, and N-glycosylation sites. Fasting was shown to decrease GHR1 expression in the liver, adipose tissue and red muscle. GH and PRL were shown to stimulate IGF expression through the ERK, PI3K/Akt, and JAK-STAT signaling pathways. GH-stimulated IGF expression was dependent on nutritional state, as GH was only able to stimulate IGF expression in fed fish. Nutritional state has no direct effect on GH-stimulated GHR expression. Serum was determined to be the mediator of the change in GH sensitivity as pre-treatment with serum from cells of an opposite nutritional state caused cells to react like the opposite nutritional state in GH-stimulated IGF expression. These findings contribute to the understanding of the actions of GH-family peptides and the mechanisms through which GH conducts its diverse actions in times of differing nutritional availability. === National Science Foundation grant IOS 0920116 to M. A. Sheridan