Effects of thyroid hormone on the GH signal transduction pathway

Abstract

Background/aim: The importance of thyroid hormone on growth and development in children iswell 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 24 h 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 effectwas not observedwhen the fibroblasts were co-incubatedwith GHand the lower concentration of T4 (250 nM). Conclusion: Combined stimulationwith 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.