Stimulation of alkaline phosphatase activity by thyroid hormone in mouse osteoblast-like cells (MC3T3-E1): a possible mechanism of hyperalkaline phosphatasia in hyperthyroidism.

In order to elucidate the mechanism of increased alkaline phosphatase (AI-P) activity of bone origin in serum of patients with hyperthyroidism, the effects of thyroid hormone on mouse osteoblast-like cells (MC3T3-E1) were studied in vitro. Triiodo-L-thyronine (T3) and thyroxine (T4) produced a dose-dependent increase in AI-P activity in the cells at minimum concentrations of 10(-10)M T3 (free T3, 5 x 10(-12) M) and 10(-8) M T4 (free T4, 8 x 10(-11) M), respectively. Scatchard analysis revealed that MC3T3-E1 cells contained nuclear binding sites specific for T3 with an apparent Kd of 120 pM (maximum number of binding sites, approximately 2500 per cell). When cells were cultured with T3 in alpha-minimal essential medium (alpha-MEM) for a prolonged period, AI-P activity also became detectable in the conditioned medium. In contrast to rat osteosarcoma cells (ROS 17/2.8), MC3T3-E1 cell growth was inhibited by T4 in a concentration-dependent manner. These findings suggest that thyroid hormone inhibits proliferation and stimulates differentiation of mouse osteoblast-like cells. Since T3 and T4 stimulate AI-P activity not only in the cells but also in the medium, we speculate that the hyper-alkaline phosphatasia frequently seen in patients with hyperthyroid Graves' disease is partly due to a direct effect of thyroid hormone on osteoblasts or osteoblast-like cells.