Igf1 and Igf2 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 Igf2 stimulates fetal and placental growth. Hepatic Igf2 production is not regulated by Gh in mammals. Little is known about the regulation of hepatic Igf2 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 (10⁻⁷ M 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 Igf2 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.

IGF-binding proteins (IGFBPs) modulate the effects of the IGFs, major stimulators of vertebrate growth and development. In mammals, IGFBP-1 inhibits the actions of IGF-I. Rapid increases in circulating IGFBP-1 occur during catabolic states. Insulin and glucocorticoids are the primary regulators of circulating IGFBP-1 in mammals. Insulin inhibits and glucocorticoids stimulate hepatocyte IGFBP-1 gene expression and production. A 22 kDa IGFBP in salmon blood also increases during catabolic states and has recently been identified as an IGFBP-1 homolog. We examined the hormonal regulation of salmon IGFBP-1 mRNA levels and protein secretion in primary cultured salmon hepatocytes. The glucocorticoid agonist dexamethasone progressively increased hepatocyte IGFBP-1 mRNA levels (eightfold) and medium IGFBP-1 immunoreactivity over concentrations comparable with stressed circulating cortisol levels (10⁻⁹–10⁻⁶ M). GH progressively reduced IGFBP-1 mRNA levels (0.3-fold) and medium IGFBP-1 immunoreactivity over physiological concentrations (5 × 10⁻¹¹–5 × 10⁻⁹ M). Unexpectedly, insulin slightly increased hepatocyte IGFBP-1 mRNA (1.4-fold) and did not change medium IGFBP-1 immunoreactivity over physiological concentrations and above (10⁻⁹–10⁻⁶ M). Triiodothyronine had no effect on hepatocyte IGFBP-1 mRNA, whereas glucagon increased IGFBP-1 mRNA (2.2-fold) at supraphysiological concentrations (10⁻⁶ M). This study suggests that the major inhibitory role of insulin in the regulation of liver IGFBP-1 production in mammals is not found in salmon. However, regulation of salmon liver IGFBP-1 production by other metabolic hormones is similar to what is found in mammals.