Effect of hyperthyroidism on circulating levels of free and total IGF-I and IGFBPs in rats

Thyroid hormones are suggested to have a permissive role in growth hormone (GH) and insulin-like growth factor I (IGF-I) action and a specific effect on plasma levels of some of the GH-independent IGF binding proteins (IGFBPs). We have investigated the effect of thyroxine (T4) administration on circulating levels of free and total (extractable) IGF-I and IGFBPs in 8-wk-old rats treated with 0, 200, 400, and 600 micrograms/kg T4, respectively. Serum free IGF-I was determined by an ultrafiltration method, serum total IGF-I after acid-ethanol extraction, and serum IGFBPs using Western ligand blotting, which yielded four distinct molecular bands: two single bands at 24 and 30 kDa and a double band at 38 and 42 kDa (38-42 kDa). After 13 days of hyperthyroidism, serum total IGF-I and the high-molecular 38-42 kDa IGFBP were unchanged, whereas the 24-kDa IGFBP and 30-kDa IGFBP increased significantly (P < 0.05). Serum free IGF-I was significantly (P < 0.05) decreased in animals treated with 400 and 600 micrograms/kg T4. In addition, free IGF-I correlated inversely (P < 0.005) with the 24-kDa IGFBP, 30-kDa IGFBP, and serum total triiodothyronine. We conclude that hyperthyroidism in rats increases the circulating low-molecular IGFBPs and induces a reduction in free IGF-I. This may provide an important regulation of IGF bioactivity by thyroid hormones.