Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Epidermis / drug effects
  • Epidermis / metabolism
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Matrix Metalloproteinases / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Organ Culture Techniques
  • Reactive Oxygen Species / metabolism
  • Skin Aging / physiology
  • Skin Diseases / drug therapy
  • Skin Diseases / pathology
  • Thyroxine / administration & dosage*
  • Thyroxine / pharmacology
  • Triiodothyronine / administration & dosage*
  • Triiodothyronine / pharmacology


  • Reactive Oxygen Species
  • Triiodothyronine
  • Matrix Metalloproteinases
  • Thyroxine