title: Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin.
abstract: 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 x 10(-11)-5 x 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.
authors.affiliation: Integrative Fish Biology Program, Northwest Fisheries Science Center, National Marine Fisheries Service, Seattle, Washington 98112, USA. piercea@hawii.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Pierce
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: L
authors.initials: L
authors.lastname: Felli
authors.forename: P
authors.initials: P
authors.lastname: Swanson
authors.forename: W W
authors.initials: WW
authors.lastname: Dickhoff
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D013006:Growth Hormone / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D011863:Radioimmunoassay / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012474:Salmon / Q000378:metabolism*; D013045:Species Specificity; D013268:Stimulation, Chemical
chemical_list: D005938:Glucocorticoids; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D003907:Dexamethasone; D013006:Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone