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Mechanism of Hypothyroidism Action on Insulin-Like Growth Factor-I and -II from Neonatal to Adult Rats: Insulin Mediates Thyroid Hormone Effects in the Neonatal Period¹

Instituto de Bioquímica (Centro Mixto Consejo Superior de Investigaciones Cientificas-Universidad Complutense de Madrid), Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain

Address all correspondence and requests for reprints to: A. M. Pascual-Leone, Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain. E-mail: apascual{at}eucmax.sim.ucm.es

The effects of thyroid hormone deficiency on serum levels and liver messenger RNA (mRNA) expression of insulin-like growth factors (IGFs) were studied in neonatal (until 20 days of life), weaned (22–37 days), and adult (72–87 days) rats, short periods (5, 10, and 15 days) after thyroidectomy (T). Serum levels and liver mRNA expression of IGF-I, plasma and pituitary GH, plasma insulin, and glycemia were measured in all populations; and serum levels and liver mRNA expression of IGF-II were measured only in the neonatal populations. Surprisingly, plasma insulin and GH and serum and liver mRNA expression of IGF-I were found elevated in T neonatal rats, and they decreased in weaned and adult rats and in neonatal rats rendered hypothyroid by mercapto-1-methylimidazole (MMI) treatment (MMI-hypothyroid). T and MMI-treatment of neonatal rats disturbed the normal pattern of progressive decrease of IGF-II with age. A positive correlation between insulin and IGF-I and a poor correlation between GH and IGF-I were found in both hypothyroid neonates (T and MMI-hypothyroid). On the contrary, a positive correlation between 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 changed in the same direction in all groups, insulin secretion in T neonatal was suppressed by streptozotocin, and insulin was given to T adult rats. The combined results of these experiments support the idea that the effects of thyroid hormones on IGF-I secretion are age-dependent, and they are mediated mainly by insulin during the neonatal period and by GH during adulthood.

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