Age-dependent adaptation of the liver thyroid status and recovery of serum levels and hepatic insulin-like growth factor-I expression in neonatal and adult diabetic rats

Abstract

The effect of treatment with thyroxine (T4) on the hepatic deiodinase (5′D-I) activity and triiodothyronine (T3) content and on insulin-like growth factor-I (IGF-I) secretion and mRNA hepatic expression were studied in neonatal and adult diabetic (D) rats and compared with 4 thyroidectomized (Tx) groups: neonatal and adult Tx rats treated or not with T4. Serum T3 and T4 decreased by 92% in both Tx populations and by 80% to 70% in D adults according to the severity of diabetes: −70 mg/kg body weight (BW) (D70) or 50 mg/kg BW (D50) of streptozotocin (STZ) injected, whereas only a 30% to 33% decrease was found in D neonates. A similar decrease of liver 5′D-I activity and T3 concentrations was found in neonatal and adult Tx rats, whereas a significant reduction in those parameters was observed only in adult diabetics, either D70 or D50, but not in D neonates. Serum levels and liver mRNA expression of IGF-I determined by ribonuclease protection assay, plasma and pituitary growth hormone (GH), plasma insulin, and glycemia were also measured in both D populations. A decrease in circulating IGF-I, previously reported for Tx adult rats, was also found in both D populations. T4 treatment recovered IGF-I and liver T3 in both Tx groups and D neonates, but not in D adults. These results show an age-dependent adaptation of the liver thyroid economy in diabetes, as hepatic 5′D-I does not respond to diabetes in neonates and IGF-I is insensitive to T4 treatment in adult diabetics and suggest a positive correlation between hepatic T3 content and IGF-I expression in conditions of diabetes and Tx.