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Journal of Endocrinology (2005) 184, 341-349    DOI: 10.1677/joe.1.05892
© 2005 Society for Endocrinology

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Metabolic hormones modulate the effect of growth hormone (GH) on insulin-like growth factor-I (IGF-I) mRNA level in primary culture of salmon hepatocytes

A L Pierce1,2, H Fukada3 and W W Dickhoff1,2

1 Integrative Fish Biology Program, Northwest Fisheries Science Center, National Marine Fisheries Service, 2725 Montlake Boulevard East, Seattle, Washington State 98112, USA
2 School of Aquatic and Fishery Sciences, University of Washington, Seattle, Washington State 98195, USA
3 Faculty of Agriculture, Kochi University, 2-5-1 Akebono-cho, Kochi, 780-8520 Japan

(Requests for offprints should be addressed to A L Pierce; Email: piercea{at}u.washington.edu)

Liver production of insulin-like growth factor-I (IGF-I) is a major point of control in the growth hormone (GH)/IGF axis, the endocrine system regulating body growth in fishes and other vertebrates. Pituitary GH stimulates hepatocyte production of IGF-I; however, in catabolic states, hepatocyte GH resistance results in decreases in liver IGF-I production. To investigate endocrine mechanisms leading to the development of hepatocyte GH resistance, we examined the regulation of IGF-I mRNA level by GH and metabolic hormones in primary culture of salmon hepatocytes. Cells were cultured in RPMI medium, and exposed to insulin (Ins, 10–6 M), glucagon (Glu, 10–6 M), triiodothyronine (T3, 10–7 M), dexamethasone (Dex, 10–6 M) and glucagon-like peptide (GLP, 10–6 M), in the presence and absence of GH (5x10–9 M). GH always increased IGF-I mRNA. None of the other hormones tested alone affected IGF-I mRNA. However, Dex, Ins and Glu reduced the response to GH. The response to GH was inhibited by Dex at concentrations of 10–12 M and above, by Ins at 10–9 M and above, and by Glu only at 10–6 M. Inhibition of GH response by glucocorticoids is found in other vertebrates. Salmon hepatocytes were very sensitive to Dex, suggesting that glucocorticoids may play an important role in salmon growth regulation even in unstressed conditions. Inhibition of GH response by Ins is the opposite of what is found in mammals and chickens, suggesting that the role of Ins in growth regulation may differ between fishes and tetrapods. To examine mechanisms for modulation of GH sensitivity, we measured hepatocyte GH receptor (GHR) mRNA levels. Ins inhibited and Dex stimulated GHR mRNA, suggesting that different mechanisms mediate the inhibition of GH response by these hormones. This study shows that glucocorticoids, Ins, and Glu induce GH resistance in cultured salmon hepatocytes.




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A L Pierce, M Shimizu, L Felli, P Swanson, and W W Dickhoff
Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin.
J. Endocrinol., November 1, 2006; 191(2): 379 - 386.
[Abstract] [Full Text] [PDF]


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L. Huo, G. Fu, X. Wang, W. K. W. Ko, and A. O. L. Wong
Modulation of Calmodulin Gene Expression as a Novel Mechanism for Growth Hormone Feedback Control by Insulin-like Growth Factor in Grass Carp Pituitary Cells
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