title: Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.
abstract: BACKGROUND
  Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion.
  
  
  OBJECTIVE
  Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis.
  
  
  METHODS
  Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h.
  
  
  RESULTS
  TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation.
  
  
  CONCLUSIONS
  These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.
authors.affiliation: Department of Dermatology, University of Luebeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Knuever
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeggeler
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Gáspár
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellwig-Burgel
authors.forename: Celine
authors.initials: C
authors.lastname: Hardenbicker
authors.forename: Balázs I
authors.initials: BI
authors.lastname: Tóth
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000328:Adult; D004734:Energy Metabolism; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009924:Organ Culture Techniques; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
chemical_list: D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone