MECHANISM OF HYPOTHYROIDISM ACTION ON INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN-LIKE GROWTH-FACTOR-II FROM NEONATAL TO ADULT RATS - INSULIN MEDIATES THYROID-HORMONE EFFECTS IN THE NEONATAL-PERIOD

The effects of thyroid hormone deficiency on serum levels and liver me ssenger RNA (mRNA) expression of insulin-like growth factors (IGFs) we re studied in neonatal (until 20 days of life), weaned (22-37 days), a nd adult (72-87 days) rats, short periods (5, 10, and 15 days) after t hyroidectomy (T). Serum levels and liver mRNA expression of IGF-I, pla sma and pituitary GH, plasma insulin, and glycemia were measured in al l populations; and serum levels and liver mRNA expression of IGF-II we re measured only in the neonatal populations. Surprisingly, plasma ins ulin and GH and serum and liver mRNA expression of IGF-I were found el evated in T neonatal rats, and they decreased in weaned and adult rats and in neonatal rats rendered hypothyroid by mercapto-1-methylimidazo le (MMI) treatment (MMI-hypothyroid). T and MMI-treatment of neonatal rats disturbed the normal pattern of progressive decrease of IGF-II wi th age. A positive correlation between insulin and IGF-I and a poor co rrelation between GH and IGF-I were found in both hypothyroid neonates (T and MMI-hypothyroid). On the contrary, a positive correlation betw een GH and IGF-I and a poor correlation between insulin and IGF-I were found for control and T adult rats. Because plasma insulin and GH cha nged in the same direction in all groups, insulin secretion in T neona tal was suppressed by streptozotocin, and insulin was given to T adult rats. The combined results of the se experiments support the idea tha t the effects of thyroid hormones on IGF-I secretion are age-dependent , and they are mediated mainly by insulin during the neonatal period a nd by GH during adulthood.