Expression and function of thyroid specific genes in human skin.

Patients affected by autoimmune thyroid diseases (AITD) are characterized by several alterations of skin function. Although skin is considered a target tissue for thyroid hormones (TH), very little is known on the molecular mechanisms involved in cutaneous manifestations during AITD. Recent data show the presence of the transcripts for the thyroid specific genes TSH receptor (TSH-R) and thyroglobulin (Tg) in immortalized keratinocytes and melanoma cells. This finding suggests that during AITD the skin could be a target of autoantibodies directed against thyroid specific antigens. To get insight into the expression and function of thyroid specific genes in skin cells, in the present study we analyzed the expression of TSH-R, Tg, sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in primary cultures of normal human keratinocytes and dermal fibroblasts by quantitative RT-PCR, in comparison with that of normal human thyrocytes (NHT). The results revealed the presence of TSH-R, Tg and NIS transcripts in both human keratinocytes and fibroblasts, while TPO mRNA was found only in keratinocytes. Immunohistochemical analysis of human healthy skin specimens confirmed the presence of TSH-R and Tg protein in keratinocytes and dermal fibroblasts. Cultured normal human keratinocytes and dermal fibroblasts were then treated with TSH (10 UI/ml) for 72 h and the effect on cell proliferation evaluated by BrdU incorporation. The results indicated the ability of TSH to significantly increase proliferation in both cell types. Moreover, TSH treatment for 2 h induced a significant increase in intracellular cAMP levels. However, differently from its action on thyrocytes, TSH did not stimulate the expression or the secretion of Tg in cultured keratinocytes and dermal fibroblasts. In conclusion, our data demonstrate that keratinocytes and fibroblasts express thyroid specific genes which may be involved in the pathogenesis of skin alterations during AITD.