Thyroid hormone stimulates alkaline phosphatase activity in cultured rat osteoblastic cells (ROS 17/2.8) through 3,5,3'-triiodo-L-thyronine nuclear receptors

Endocrinology. 1987 May;120(5):1873-81. doi: 10.1210/endo-120-5-1873.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism*
  • Animals
  • Cell Division / drug effects
  • Cell Line
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Hydrocortisone / pharmacology
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology*
  • Rats
  • Receptors, Thyroid Hormone / physiology*
  • Thyroid Hormones / pharmacology*
  • Thyroxine / pharmacology
  • Triiodothyronine / metabolism
  • Triiodothyronine / pharmacology
  • Triiodothyronine, Reverse / pharmacology

Substances

  • Receptors, Thyroid Hormone
  • Thyroid Hormones
  • Triiodothyronine
  • Dactinomycin
  • Triiodothyronine, Reverse
  • Cycloheximide
  • Alkaline Phosphatase
  • Thyroxine
  • Hydrocortisone