Meeting Abstract

2.8  Jan. 4  Metabolic hormones directly regulate insulin-like growth factor-2 mRNA level in primary cultured salmon hepatocytes PIERCE, AL*; DICKEY, JT; SWANSON, P; DICKHOFF, WW; Univ Hawaii; Univ Washington; Nat Mar Fish Svc; Univ Washington piercea@hawaii.edu

Insulin-like growth factors (IGF-1 and IGF-2) stimulate growth and development of vertebrates. Both IGFs are expressed widely; however, circulating IGFs are produced by the liver. In mammals, IGF-1 stimulates postnatal growth, and is chiefly regulated by growth hormone (GH). IGF-2, in contrast, acts mainly during placental development, and is not regulated by GH or other metabolic hormones in adult mammals. IGF-2 appears to play a greater role in postembryonic growth regulation in fishes, insofar as it responds to GH and metabolic status. However, little is known about the hormonal regulation of hepatic IGF-2 production in non-mammalian vertebrates. We examined the regulation of IGF-2 mRNA level by metabolic hormones in primary cultured salmon hepatocytes. Insulin, the glucocorticoid agonist dexamethasone (dex), and GH increased, whereas glucagon and triiiodothyronine (T3) decreased IGF-2 mRNA levels. In concentration-response studies, insulin was stimulatory at the lowest concentration tested (10-9 M), dex at concentrations comparable to stressed circulating cortisol (10-8 M and above), and GH at physiological concentrations (2.5 x 10-10 M and above). The effects of insulin, dex, and T3 were additive with that of GH, whereas stimulation by GH was dominant over suppression by glucagon. These results show that IGF-2 is directly regulated by metabolic hormones in salmon hepatocytes, unlike IGF-1, which is regulated only by modulation of sensitivity to GH. Further, the strong regulation of IGF-2 by metabolic hormones in salmon hepatocytes suggests that hepatic IGF-2 has an important function in postembryonic fishes. (Supported by NRI Competitive Grants 2003-35206-13631, 2006-35206-16447 from the USDA CSREES)