Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro.
Thyroid hormone plays a major role in the regulation of bone metabolism but the mechanism by which this is accomplished is not clear. Interactions of thyroid hormone with the growth hormone/insulin-like growth factors (IGFs) axis suggest an alternate pathway of action for triiodothyronine (T(3)) on bone formation, besides direct effects. The present study investigates the influence of T(3) on IGF-1, IGF-2, IGF-1 receptor (IGF-1R), and IGF binding protein (IGFBP) transcripts, and on IGF-1 action in human osteoblastic cells (hOB) under serum-free culture conditions. No influence of T(3) on IGF-1, IGF-2, IGFBP-3, or IGFBP-4 mRNA levels in hOB was observed. However, T(3) at concentrations of 10(-8) mol/L and 10(-7) mol/L increased IGF-1R mRNA levels in a dose-dependent manner (p < 0.01) and enhanced IGFBP-5 mRNA levels at a concentration of 10(-7) mol/L (p < 0.05), as assessed by reverse transcriptase-polymerase chain reaction. Correspondingly, Scatchard analysis of [(125)I]-IGF-1 binding revealed that T(3) at 10(-7) mol/L increased the number of IGF-1 binding sites in hOB, with small changes in receptor affinity. In addition, a synergistic effect of T(3) and IGF-1 on hOB proliferation was found (p < 0.05). We conclude that IGF-1R and IGFBP-5 are thyroid hormone target genes in human osteoblasts, whereas IGF-1 mRNA expression itself appears not to be regulated by T(3) in hOB. However, T(3) stimulates IGF-1R mRNA expression as well as IGF-1 binding and IGF-1 induced cell proliferation in osteoblasts, thus suggesting thyroid hormone may potentiate the effect of IGF-1 at the receptor level. This may contribute to the positive effects of thyroid hormone on bone formation, which, in addition, may be modulated by increased IGFBP-5 expression.
Pepene
C E
CE
Department of Internal Medicine I, University of Heidelberg, Heidelberg, Germany. carmenpepene@usa.net
Kasperk
C H
CH
Pfeilschifter
J
J
Börcsök
I
I
Gozariu
L
L
Ziegler
R
R
Seck
T
T
D001483:Base Sequence; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D017931:DNA Primers; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014284:Triiodothyronine / Q000502:physiology*
D017077:Culture Media, Conditioned; D017931:DNA Primers; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D014284:Triiodothyronine; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1