TSH receptor and thyroid-specific gene expression in human skin

Experimental evidence suggests that in autoimmune thyroid diseases (AITDs) the skin is a target of autoantibodies against thyroid-specific antigens; however, the role of these autoantibodies in skin alterations remains unclear. To gain insight into the function of nominally thyroid-specific genes in skin, we analyzed the expression of thyroid-stimulating hormone-receptor (TSH-R), thyroglobulin (Tg), sodium iodide symporter (NIS), and thyroperoxidase (TPO) genes in normal human skin biopsies and cultured primary keratinocytes and dermal fibroblasts. The results revealed the presence of all the transcripts in skin biopsies. However, in keratinocytes and fibroblasts, only TSH-R messenger RNA was always detected. Western blot and immunohistochemical analyses of skin specimens confirmed the presence of TSH-R protein in keratinocytes and fibroblasts. Moreover, TSH treatment induced the proliferation of cultured keratinocytes and fibroblasts and increased keratinocyte intracellular cAMP. Finally, affinity-purified IgGs from serum of patients affected by Graves' disease, but not by chronic lymphocytic thyroiditis, stimulated cAMP accumulation in cultured keratinocytes, as well as their proliferation. In conclusion, the expression of thyroid-specific genes in cultured keratinocytes and fibroblasts and the mitogenic effects of TSH and IgGs on these cells support the concept that autoantibodies against thyroid-specific antigens may contribute to cutaneous symptoms in AITDs.