Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles.
Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable.
Department of Dermatology, University of Luebeck, Luebeck, Germany.
Silvia
S
Vidali
Department of Dermatology, University of Luebeck, Luebeck, Germany.
Jana
J
Knuever
Institute of Physical Chemistry, TU Bergakademie, Freiberg, Germany.
Johannes
J
Lerchner
Henkel Beauty Care, Henkel AG and Co. KGaA, Dusseldorf, Germany.
Melanie
M
Giesen
Department of Physiology, University of Debrecen, Debrecen, Hungary.
Tamás
T
Bíró
Department of Anatomy, University of Luebeck, Luebeck, Germany.
Matthias
M
Klinger
Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
Barbara
B
Kofler
Klinik Dr Koslowski, Munich, Germany.
Wolfgang
W
Funk
Department of Dermatology, University of Luebeck, Luebeck, Germany.
Burkhard
B
Poeggeler
Department of Dermatology, University of Luebeck, Luebeck, Germany; Institute of Inflammation and Repair, University of Manchester, and The Dermatology Centre, Salford Royal NHS Trust, Manchester, UK. Electronic address: ralf.paus@uksh.de.
Ralf
R
Paus
D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012535:Scalp / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D013965:Thyroidectomy; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology
D013963:Thyroid Hormones; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine