Pierce A L, Shimizu M, Felli L, Swanson P, Dickhoff W W
Integrative Fish Biology Program, Northwest Fisheries Science Center, National Marine Fisheries Service, Seattle, Washington 98112, USA.
J Endocrinol. 2006 Nov;191(2):379-86. doi: 10.1677/joe.1.06986.
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.
胰岛素样生长因子结合蛋白（IGFBPs）可调节胰岛素样生长因子（IGFs）的作用，而IGFs是脊椎动物生长和发育的主要刺激因子。在哺乳动物中，IGFBP-1可抑制IGF-I的作用。在分解代谢状态下，循环中的IGFBP-1会迅速增加。胰岛素和糖皮质激素是哺乳动物循环中IGFBP-1的主要调节因子。胰岛素起抑制作用，而糖皮质激素则刺激肝细胞IGFBP-1基因的表达和产生。鲑鱼血液中的一种22 kDa的IGFBP在分解代谢状态下也会增加，最近被鉴定为IGFBP-1的同源物。我们研究了原代培养的鲑鱼肝细胞中鲑鱼IGFBP-1 mRNA水平和蛋白质分泌的激素调节。糖皮质激素激动剂地塞米松在与应激时循环皮质醇水平相当的浓度范围内（10^(-9)-10^(-6) M），可使肝细胞IGFBP-1 mRNA水平逐渐升高（8倍），并使培养基中IGFBP-1免疫反应性增强。生长激素（GH）在生理浓度范围内（5×10^(-11)-5×10^(-9) M）可使IGFBP-1 mRNA水平逐渐降低（0.3倍），并使培养基中IGFBP-1免疫反应性减弱。出乎意料的是，胰岛素在生理浓度及以上（10^(-9)-10^(-6) M）时，可使肝细胞IGFBP-1 mRNA略有增加（1.4倍），但对培养基中IGFBP-1免疫反应性无影响。三碘甲状腺原氨酸对肝细胞IGFBP-1 mRNA无影响，而胰高血糖素在超生理浓度（10^(-6) M）时可使IGFBP-1 mRNA增加（2.2倍）。这项研究表明，在鲑鱼中未发现胰岛素在调节哺乳动物肝脏IGFBP-1产生方面的主要抑制作用。然而，其他代谢激素对鲑鱼肝脏IGFBP-1产生的调节与在哺乳动物中发现的情况相似。
