Effects of thyroid hormone on the GH signal transduction pathway.
OBJECTIVE
The importance of thyroid hormone on growth and development in children is well recognized. In addition, linear growth is highly dependent on the response of peripheral tissues to growth hormone, a process known as GH sensitivity, but little is known about the possible effects of T4 on this process.


METHODS
We determined the effect of stimulation with recombinant human GH (rhGH; 200 ng/mL) alone or in combination with two different concentrations of T4 (250 nM and 500 nM for 24 h) on JAK2 and STAT5 activation in skin fibroblast cultures obtained from prepubertal boys with normal height.


RESULTS
JAK2 and STAT5 were activated under co-incubation with T4 (at both concentrations) and rhGH in the non-nuclear fraction of the fibroblasts. In addition, after 24h of co-incubation with rhGH and T4 (500 nM), we observed an increase in phospho-STAT5 in the nuclear fraction, when compared to GH and T4 stimulation alone. This effect was not observed when the fibroblasts were co-incubated with GH and the lower concentration of T4 (250 nM).


CONCLUSIONS
Combined stimulation with GH and T4 at a concentration of 500 nM increases synergistically nuclear phospho-STAT5 in skin fibroblasts, which may amplify tissue sensitivity to GH. These findings may help to explain the effect of T4 administration on growth velocity in some children with idiopathic short stature.
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile. Electronic address: pauocaranza@gmail.com.
Paula
P
Ocaranza
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
Juan Javier
JJ
Lammoglia
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
Germán
G
Iñiguez
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
Rossana
R
Román
Institute of Maternal and Child Research, School of Medicine, University of Chile, Santiago, Chile.
Fernando
F
Cassorla
D015153:Blotting, Western; D001827:Body Height / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology*
D050799:STAT5 Transcription Factor; D013963:Thyroid Hormones; D019382:Human Growth Hormone; C507924:JAK2 protein, human; D053614:Janus Kinase 2
GH signal transduction; Skin fibroblasts; Thyroid hormone