Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats

The effrects of different doses of thyroxine (T-4) delivered by injection o r s.c. pellet implantation on alterations of the IGF/IGF binding protein (I GFBP) system were studied in neonatal and adult thyroidectomized (Tx) rats. Body weight, blood glucose, plasma insulin, TSH and GH and pituitary GH co ntent, as well as serum IGF-I, IGF-II, IGFBP-1, -2 and -3 and their liver m RNA expression were assayed. Pellet implantation with the smaller dose of T -4 (1(.)5 mug/100 g body weight (b.w.) per day) in Tx neonatal rats decreas ed serum IGF-I, -II and the 30 kDa complex of IGFBPs (IGFBP-1 and -2), and increased serum IGFBP-3. Only the larger dose of T-4 (3 mug/100 g b.w. per day) recovered liver mRNA expression of IGF-I and ensured euthyroid stat-us as shown by the normalized levels of plasma. TSH. The rapid increase of bo dy weight and serum GI-I after T-4 administration indicated a high sensitiv ity to T-4 during the neonatal period. Serum and liver mRNA expression of I GFs and plasma insulin and CH recovered in adult Tx rats after pellet impla ntation of 175 mug/100g b.w. per day throughout 10 days. The continuous rep lacement of T-4 by pellet stems to be the most suitable method for thyroid rehabilitation. A very good correlation was found between insulin and IGF-I I in Tx neonates treated with T-4 but not between insulin and IGF-I in Tx a dults. IGFBP-2 seems to be up-regulated by T-4 deprivation in neonatal and adult rats. Finally, a good correlation as well as a partial correlation we re found between IGFs and thyroid hormones in both neonatal and adult Tx po pulations, suggesting a direct effect in vitro of T-4 On the hepatic secret ion of IGFs, as previously suggested in vitro.