Dexamethasone decreases serum and liver IGF-I and maintains liver IGF-I mRNA in parenterally fed rats

Insulin-like growth factor-I (IGF-I) gene expression is regulated by nutritional and hormonal factors. High-dose glucocorticoids decrease food intake, and this confounds studies addressing glucocorticoid effects on IGF-I gene regulation. We investigated alterations in the hepatic IGF-I endocrine system induced by a catabolic dose of dexamethasone (Dex) in rats given adequate nutrition by continuous infusion of total parenteral nutrition (TPN) solution with or without IGF-I administration. The four TPN groups included control, +Dex, +IGF-I, and +IGF-I + Dex (n = 9-11/group). Dex induced a 12% loss of body weight in association with a 50% decrease in hepatic immunoreactive IGF-I, a 10% decrease in serum IGF-I, and no change in steady-state liver IGF-I mRNA or growth hormone (GH) receptor binding. Exogenous IGF-I increased serum IGF-I, attenuated Dex-induced catabolism, and did not reduce hepatic levels of IGF-I and IGF-I mRNA despite decreased serum GH. These data suggest that Dex-induced catabolism is associated with downregulation of the hepatic IGF-I endocrine system at the translational or posttranslational level when adequate nutrition is provided.