Thyroid-stimulating hormone, a novel, locally produced modulator of human epidermal functions, is regulated by thyrotropin-releasing hormone and thyroid hormones.
Several elements of the hypothalamic-pituitary-thyroid axis (HPT) reportedly are transcribed by human skin cell populations, and human hair follicles express functional receptors for TSH. Therefore, we asked whether the epidermis of normal human skin is yet another extrathyroidal target of TSH and whether epidermis even produces TSH. If so, we wanted to clarify whether intraepidermal TSH expression is regulated by TRH and/or thyroid hormones and whether TSH alters selected functions of normal human epidermis in situ. TSH and TSH receptor (TSH-R) expression were analyzed in the epidermis of normal human scalp skin by immunohistochemistry and PCR. In addition, full-thickness scalp skin was organ cultured and treated with TSH, TRH, or thyroid hormones, and the effect of TSH treatment on the expression of selected genes was measured by quantitative PCR and/or quantitative immunohistochemistry. Here we show that normal human epidermis expresses TSH at the mRNA and protein levels in situ and transcribes TSH-R. It also contains thyrostimulin transcripts. Intraepidermal TSH immunoreactivity is up-regulated by TRH and down-regulated by thyroid hormones. Although TSH-R immunoreactivity in situ could not be documented within the epidermis, but in the immediately adjacent dermis, TSH treatment of organ-cultured human skin strongly up-regulated epidermal expression of involucrin, loricrin, and keratins 5 and 14. Thus, normal human epidermis in situ is both an extrapituitary source and (possibly an indirect) target of TSH signaling, which regulates defined epidermal parameters. Intraepidermal TSH expression appears to be regulated by the classical endocrine controls that determine the systemic HPT axis.
Bodó
Eniko
E
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Kany
Benedikt
B
Gáspár
Erzsébet
E
Knüver
Jana
J
Kromminga
Arno
A
Ramot
Yuval
Y
Bíró
Tamás
T
Tiede
Stephan
S
van Beek
Nina
N
Poeggeler
Burkhard
B
Meyer
Katja C
KC
Wenzel
Björn E
BE
Paus
Ralf
R
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012535:Scalp / Q000187:drug effects / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D053547:Keratin-14; D053555:Keratin-5; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; C064554:loricrin; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; C032253:involucrin; D013972:Thyrotropin; D013974:Thyroxine