Background/aimThe 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. MethodsWe determined the effect of stimulation with recombinant human GH (rhGH; 200ng/mL) alone or in combination with two different concentrations of T4 (250nM and 500nM for 24h) on JAK2 and STAT5 activation in skin fibroblast cultures obtained from prepubertal boys with normal height. ResultsJAK2 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 (500nM), 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 (250nM). ConclusionCombined stimulation with GH and T4 at a concentration of 500nM 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.