title: Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis.
abstract: Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L). Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria. Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity. Increased mitochondrial function can correlate with increased reactive oxygen species production, DNA damage, and accelerated tissue aging. However, THs neither raised reactive oxygen species production or matrix metalloproteinase-1, -2 and -9 activity nor decreased sirtuin1 (Sirt1) immunoreactivity. Instead, triiodothyronine increased sirtuin-1, fibrillin-1, proliferator-activated receptor-gamma 1-alpha (PGC1α), collagen I and III transcription, and thyroxine decreased cyclin-dependent kinase inhibitor 2A (p16(ink4)) expression in organ-cultured human skin. Moreover, TH treatment increased intracutaneous fibrillin-rich microfibril and collagen III deposition and decreased mammalian target of rapamycin (mTORC1/2) expression ex vivo. This identifies THs as potent endocrine stimulators of mitochondrial function in human epidermis, which down-regulates rather than enhance the expression of skin aging-related biomarkers ex vivo. Therefore, topically applied THs deserve further exploration as candidate agents for treating skin conditions characterized by reduced mitochondrial function.
authors.affiliation: Department of Dermatology, University of Luebeck, Luebeck, Germany; Research Program for Receptor Biochemistry and Tumor Metabolism, Laura Bassi Centre of Expertise-THERAPEP, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidali
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Chéret
authors.affiliation: Henkel Beauty Care, Henkel AG and Co. KgaA, Düsseldorf, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Giesen
authors.affiliation: Department of Dermatology, University of Luebeck, Luebeck, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Haeger
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Majid
authors.initials: M
authors.lastname: Alam
authors.affiliation: Center for Dermatology Research, University of Manchester, Manchester, UK.
authors.forename: Rachel E B
authors.initials: REB
authors.lastname: Watson
authors.affiliation: Center for Dermatology Research, University of Manchester, Manchester, UK.
authors.forename: Abigail K
authors.initials: AK
authors.lastname: Langton
authors.affiliation: Department of Anatomy, University of Luebeck, Luebeck, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.affiliation: Department of Dermatology, University of Luebeck, Luebeck, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Knuever
authors.affiliation: Klinik Dr Funk, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Funk
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Laura Bassi Centre of Expertise-THERAPEP, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
authors.affiliation: Department of Dermatology, University of Münster, Münster, Germany; Center for Dermatology Research, University of Manchester, Manchester, UK. Electronic address: ralf.paus@manchester.ac.uk.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000279:Administration, Cutaneous; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D017382:Reactive Oxygen Species / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology; D012871:Skin Diseases / Q000188:drug therapy / Q000473:pathology; D013974:Thyroxine / Q000008:administration & dosage* / Q000494:pharmacology; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014284:Triiodothyronine; D020782:Matrix Metalloproteinases; D013974:Thyroxine