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J Invest Dermatol. 2016 Oct;136(10):2003-2012. doi: 10.1016/j.jid.2016.05.118. Epub 2016 Jun 25.

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis.

Author information

1
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.
2
Department of Dermatology, University of Münster, Münster, Germany.
3
Henkel Beauty Care, Henkel AG and Co. KgaA, Düsseldorf, Germany.
4
Department of Dermatology, University of Luebeck, Luebeck, Germany.
5
Center for Dermatology Research, University of Manchester, Manchester, UK.
6
Department of Anatomy, University of Luebeck, Luebeck, Germany.
7
Klinik Dr Funk, Munich, Germany.
8
Research Program for Receptor Biochemistry and Tumor Metabolism, Laura Bassi Centre of Expertise-THERAPEP, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
9
Department of Dermatology, University of Münster, Münster, Germany; Center for Dermatology Research, University of Manchester, Manchester, UK. Electronic address: ralf.paus@manchester.ac.uk.

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.

PMID:
27349864
DOI:
10.1016/j.jid.2016.05.118
[Indexed for MEDLINE]
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