11 EFFECTS OF THYROID HORMONE ON GROWTH HORMONE RECEPTOR (GHR) AND IGF-i EXPRESSION

Hypothyroidism induces growth retardation and decreases the circulating concentrations of GH and IGF-I. To study the effects of thyroid hormone on GHR and IGF-I expression, we measured rat liver and kidney GHR and IGF-I mRNA levels by solution hybridization RNase protection assay. Three to six 21 day-old castrated male rats per group were given either pure water or 0.025% methimazole in their drinking water, and subcutaneous pellet containing either placebo or thyroxine (T4) 2.5 mg. After 13 days, the animals were sacrificed. Serum free T4 and IGF-I levels were determined by RIA. Liver and kidney GHR and IGF-I, mRNA were measured by solution hybridization using specific antisense riboprobes. Protected bands corresponding to GHR and IGF-I mRNA were quantified using a Phosphorlmager. Hypothyroid rats grew slower than controls. IGF-I mRNA levels were reduced in liver but not in kidney, and were normalized after thyroxine treatment. GH receptor mRNA levels were increased in liver of rats receiving methimazole, and were decreased in the kidney of hypothyroid rats. These findings suggest that the reduction in IGF-I synthesis observed in hypothyroid rats is not mediated though a decrease in liver GH receptor expression.