| Summary: | Growth hormone (GH) regulates several physiologic processes in vertebrates, including the promotion of growth, an anabolic process, and mobilization of stored lipid, a catabolic process. Here, we used rainbow trout (Oncorhynchus mykiss) as a model to examine the nutritional programming required for the disparate metabolic actions of GH, specifically lipolysis. Juvenile trout were exposed to fed and fasting regimens in vivo and subsequent hormone treatment in vitro. We used real-time quantitative-PCR to measure levels of mRNA expression of Hormone-sensitive lipase 1 (HSL1) and HSL2 in liver, muscle, and adipose tissue. We used Western blotting to investigate the signaling pathways affected by nutritional state and activated by GH (e.g., JAK-STAT, MAPK, PI3K-AKT, PKC-PLC).
In vivo, fasting retarded growth and activated lipolysis through enhanced HSL mRNA expression and protein activation. Moreover, fasting resulted in phosphorylation of ERK and PKC but not Akt, JAK2, and STAT5 in adipose tissue, liver, and muscle. In vitro, GH stimulated glycerol release, HSL mRNA expression, and HSL phosphorylation in a time- and concentration- related manner but only in hepatocytes isolated from fasted and not fed fish. Moreover, these actions were dependent upon PKC-PLC and MAPK-ERK activation but not JAK-STAT or PI3K-Akt action. Nutritional state, insulin, and insulin-like growth factor I (IGF-I) pretreatments affect lipolytic responsiveness in hepatocyte. When in a fed state, with high levels of insulin and IGF, GH links to JAK-STAT pathways to promote growth. In a fasted state, with low levels of insulin and IGF, GH links to lipolysis through PKC and ERK activation. The findings of this dissertation indicate that nutritional status of an organism may mediate the pleiotropic actions of GH by linking it to unique intracellular signaling pathways. In the circumstances of fasting, GH stimulates lipolysis through PKC and ERK activation. === National Science Foundation (NSF) === ND EPSCoR === North Dakota State University. Deptartment of Biological Sciences
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