Human female hair follicles are a direct, nonclassical target for thyroid-stimulating hormone.
Pituitary thyroid-stimulating hormone (TSH) regulates thyroid hormone synthesis via receptors (TSH-R) expressed on thyroid epithelial cells. As the hair follicle (HF) is uniquely hormone-sensitive and, hypothyroidism with its associated, increased TSH serum levels clinically can lead to hair loss, we asked whether human HFs are a direct target for TSH. Here, we report that normal human scalp skin and microdissected human HFs express TSH-R mRNA. TSH-R-like immunoreactivity is limited to the mesenchymal skin compartments in situ. TSH may alter HF mesenchymal functions, as it upregulates alpha-smooth muscle actin expression in HF fibroblasts. TSH-R stimulation by its natural ligand in organ culture changes the expression of several genes of human scalp HFs (for example keratin K5), upregulates the transcription of classical TSH target genes and enhances cAMP production. Although the functional role of TSH in human HF biology awaits further dissection, these findings document that intracutaneous TSH-Rs are fully functional in situ and that HFs of female individuals are direct targets for nonclassical, extrathyroidal TSH bioregulation. This suggests that organ-cultured scalp HFs provide an instructive and physiologically relevant human model for exploring nonclassical functions of TSH, in and beyond the skin.
Bodó
Enikö
E
Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Lübeck, Germany.
Kromminga
Arno
A
Bíró
Tamás
T
Borbíró
István
I
Gáspár
Erzsébet
E
Zmijewski
Michal A
MA
van Beek
Nina
N
Langbein
Lutz
L
Slominski
Andrzej T
AT
Paus
Ralf
R
D000199:Actins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D053555:Keratin-5 / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism; D012535:Scalp / Q000166:cytology* / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D013954:Thyroglobulin / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000494:pharmacology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
D000199:Actins; D053555:Keratin-5; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP