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Thyroid hormone 5′‐deiodinase activity, nuclear binding, and effects on mitogenesis in umr‐106 osteoblastic osteosarcoma cells
Author(s) -
Lebron Barbara A.,
Pekary A. Eugene,
Mirell Carol,
Hahn Theodore J.,
Hershman Jerome M.
Publication year - 1989
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650040207
Subject(s) - medicine , endocrinology , osteoblast , hormone , triiodothyronine , thyroid hormone receptor , thyroid , cell growth , biology , cell nucleus , osteosarcoma , deiodinase , in vivo , dna synthesis , cell culture , cell , in vitro , nucleus , microbiology and biotechnology , cancer research , biochemistry , genetics
The hyperthyroid state in vivo is associated with an increase in osteoblast number and activity, suggesting that thyroid hormone may stimulate osteoblast replication and function. We therefore examined the effects of T 3 (16–1170 pM) on replication rate as assessed by cell counts in UMR‐106 osteoblastic osteosarcoma cells cultured for 5–10 days in medium supplemented with 10% hormone‐stripped fetal calf serum (FCS). Despite the virtual absence of thyroid hormone in the control medium (total T 3 concentration, 0.02 ng/ml), the addition of T 3 in concentrations to 1000 pM did not increase the cell replication rate. At higher T 3 concentrations, a slight decrease in growth rate was observed. No significant 5′‐monodeiodinase activity was detected in UMR‐106 cell homogenates. However, nuclear binding of T 3 was demonstrated in intact cells. A high‐affinity nuclear binding component was identified with a K a of 2.6 × 10 10 M −1 and a maximum binding capacity of 7.7 pg T 3 per mg DNA, equivalent to 51 binding sites per cell nucleus. A lower affinity nuclear T 3 binding component with a K a of 1.8 × 10 9 M −1 was also identified. Thus, despite the presence of nuclear T 3 receptors, UMR‐106 cells do not exhibit a mitogenic response to T 3 .