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Date of Award
2017
Publisher
North Dakota State University
Document Type
Dissertation
Degree Awarded
Doctor of Philosophy (PhD)
Program
Cellular and Molecular Biology
Department
Cellular and Molecular Biology
College
Graduate and Interdisciplinary Studies
Faculty Advisor
Reed, Wendy L.
Description
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.
Recommended Citation
Walock, Chad Napoleon, "The Discovery of a Novel Growth Hormone Receptor and the Nutritional Regulation of the Growth Related Actions of Growth Hormone" (2017). Cellular and Molecular Biology. 8.
https://digitalcommons.ndsu.edu/cellular-molecular-biology/8
Rights
NDSU policy 190.6.2
Rights Link
https://www.ndsu.edu/fileadmin/policy/190.pdf
Author ORCID Identifier
0000-0001-5191-8178
Handle Identifier
https://hdl.handle.net/10365/27453