Endocrine growth regulation in salmon: mechanisms of nutritional control of the growth axis

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Endocrine growth regulation in salmon: mechanisms of nutritional control of the growth axis

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Title: Endocrine growth regulation in salmon: mechanisms of nutritional control of the growth axis
Author: Pierce, Andrew L
Abstract: Vertebrate growth is regulated by the growth endocrine axis, which consists of pituitary growth hormone (GH), liver insulin-like growth factor-I (IGF-I), and IGF binding proteins (IGFBPs). Studies were conducted to characterize mechanisms of nutritional regulation of the salmon growth axis. The time course of the growth axis response to Fasting, Maximum, or Control rations was assessed. GH increased in Fasted salmon. Fasted GH first increased moderately (days 1--12) and then dramatically (days 15--29), suggesting that the GH response to fasting has two phases. Plasma IGF-I and 41-kDa IGFBP (putative IGFBP-3) were lower in Fasted salmon from day 4 onward, suggesting that liver GH resistance developed within 4 days. Liver IGF-I mRNA was lower in Fasted salmon from day 6 onward, and correlated with plasma IGF-I, suggesting that liver IGF-I production regulates plasma IGF-I level. Basal plasma insulin was lower in Fasted salmon from day 6 onward, but did not respond strongly to fasting.Primary hepatocyte culture was used to study the regulation of salmon liver IGF-I production. Hepatocyte IGF-I mRNA decreased over 48 hours in culture. GH always stimulated IGF-I mRNA. The IGF-I mRNA response to GH was biphasic, declining from maximal at 5 x 10-7 M GH, suggesting that GH signal transduction in salmon is similar to mammals. Medium IGF-I (5 x 10-9 M), insulin (10-6 M), glucagon (10-6 M), triiodothyronine (10-7 M), dexamethasone (10-6 M), and glucagon-like peptide (10-6 M), did not affect basal IGF-I mRNA. However, dexamethasone, insulin, and glucagon reduced the IGF-I mRNA response to GH, indicating that hepatocyte GH sensitivity is regulated by metabolic hormones in salmon. Dexamethasone inhibited the GH response at concentrations of 10 -12 M and above, insulin at 10-9 M and above, and glucagon only at pharmacological concentrations (10 -6 M). Inhibition of IGF-I production by dexamethasone is a mechanism for growth inhibition by stress. The sensitivity of salmon hepatocytes to dexamethasone suggests glucocorticoids tonically regulate the salmon growth axis. Inhibition by insulin is the inverse of what is found in mammals, suggesting that the role of insulin in growth regulation differs between salmon and mammals.
Description: Thesis (Ph. D.)--University of Washington, 2003
URI: http://hdl.handle.net/1773/5311

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