Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17/2.8) through 3,5,3'-triiodo-L-thyronine nuclear receptors.
To investigate the increased alkaline phosphatase activity of bone origin in patients with hyperthyroidism, we studied the thyroid hormone effects on alkaline phosphatase activity in a clonal rat osteoblastic cell line (ROS 17/2.8). T4 and T3 increased alkaline phosphatase activity in ROS 17/2.8 cells in a dose-dependent manner. The minimal effective T4 and T3 concentrations in medium containing 10% thyroid hormone-depleted fetal calf serum were 10(-8) M (free T4, 8 X 10(-11) M) and 10(-9) M (free T3, 4 X 10(-11) M), respectively. ROS 17/2.8 cells possessed high affinity, low capacity nuclear receptors specific for T3 [dissociation constant (Kd) approximately 150 pM; maximal binding capacity, approximately 2000 T3 binding sites per nucleus]. The relative affinity of T3, T4, rT3, MIT, and DIT were in good agreement with their biological activity. These findings suggest that rat osteoblast-like cells contain T3 nuclear receptors and that alkaline phosphatase activity is stimulated by thyroid hormone via a nuclear receptor-mediated process at free thyroid hormone concentrations attainable in patients with Graves' disease.
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology; D014285:Triiodothyronine, Reverse / Q000494:pharmacology
D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D003609:Dactinomycin; D014285:Triiodothyronine, Reverse; D003513:Cycloheximide; D000469:Alkaline Phosphatase; D013974:Thyroxine; D006854:Hydrocortisone