Metabolic hormones regulate basal and growth hormone-dependent igf 2 mRNA level in primary cultured coho salmon hepatocytes: Effects of insulin, glucagon, dexamethasone, and triiodothyronine

Abstract

Igf1 and Igf 2 stimulate growth and development of vertebrates. Circulating Igfs are produced by the liver. In mammals, Igf1 mediates the postnatal growth-promoting effects of growth hormone (Gh), whereas Igf 2 stimulates fetal and placental growth. Hepatic Igf 2 production is not regulated by Gh in mammals. Little is known about the regulation of hepatic Igf 2 production in nonmammalian vertebrates. We examined the regulation of igf2 mRNA level by metabolic hormones in primary cultured coho salmon hepatocytes. Gh, insulin, the glucocorticoid agonist dexamethasone (Dex), and glucagon increased igf2 mRNA levels, whereas triiodothyronine (T3) decreased igf2 mRNA levels. Gh stimulated igf2 mRNA at physiological concentrations (0.25×10-9 M and above). Insulin strongly enhanced Gh stimulation of igf2 at low physiological concentrations (10-11 M and above), and increased basal igf2 (10-8 M and above). Dex stimulated basal igf2 at concentrations comparable to those of stressed circulating cortisol (10-8 M and above). Glucagon stimulated basal and Gh-stimulated igf2 at supraphysiological concentrations (10-7M and above), whereas T3 suppressed basal and Gh-stimulated igf2 at the single concentration tested (10-7 M). These results show that igf2 mRNA level is highly regulated in salmon hepatocytes, suggesting that liver-derived Igf 2 plays a significant role in salmon growth physiology. The synergistic regulation of igf2 by insulin and Gh in salmon hepatocytes is similar to the regulation of hepatic Igf1 production in mammals. © 2010 Society for Endocrinology.