Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-E1

Thyroid hormones are known to affect skeletal growth and maturation by influencing both bone resorption and bone formation. Their exact mechanism of action, however, is still unknown. Local factors such as prostaglandins, TGF-beta or IGF-I were suggested to mediate their effects. Thyroid hormones were reported to stimulate expression of IGF-I mRNA in liver and kidney and to increase IGF-I release from bone organ cultures and osteoblast-like cells. Therefore we studied the effect of thyroid hormones on IGF-I mRNA expression in MC3T3-E1 cells. The cells were grown in culture for 5 to 7 days and treated with triiodothyronine (10(-11)-10(-6) M) and thyroxin (10(-6) M) for 1-24 h. Cellular mRNA was isolated and subjected to Northern hybridization. The amount of IGF-I mRNA, which is already expressed in this cell line under control conditions, was markedly enhanced by T3 and T4. This effect was found to be dose-dependent with a maximum at 10(-7) M and could already be seen after 3 h increasing up to 24 h. Our findings indicate that IGF-I expression in osteoblasts is directly regulated by thyroid hormones. We conclude that IGF-I expression belongs to the phenotypic characteristics of mature osteoblasts, and that thyroid hormones play an important role in differentiation of MC3T3-E1 cells along the osteoblastic lineage.