Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis

Jana Knuever, Burkhard Poeggeler, Erzsébet Gáspár, Matthias Klinger, Thomas Hellwig-Burgel, Celine Hardenbicker, Balázs I. Tóth, Tamás Bíró, Ralf Paus

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Context: 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.

Original languageEnglish (US)
Pages (from-to)978-986
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

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Mitochondria
Thyrotropin-Releasing Hormone
Transcription
Thyroid Hormones
Epidermis
Skin
Thyrotropin Releasing Hormone Receptors
Oxygen
Enzyme activity
Organelle Biogenesis
Mitochondrial DNA
Genes
Hormones
Transmission electron microscopy
Oxygen Consumption
Electron Transport Complex I
Proteins
Mitochondrial Genes
Electron Transport
Transmission Electron Microscopy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Knuever, J., Poeggeler, B., Gáspár, E., Klinger, M., Hellwig-Burgel, T., Hardenbicker, C., ... Paus, R. (2012). Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis. Journal of Clinical Endocrinology and Metabolism, 97(3), 978-986. https://doi.org/10.1210/jc.2011-1096

Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis. / Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I.; Bíró, Tamás; Paus, Ralf.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 3, 01.03.2012, p. 978-986.

Research output: Contribution to journalArticle

Knuever, J, Poeggeler, B, Gáspár, E, Klinger, M, Hellwig-Burgel, T, Hardenbicker, C, Tóth, BI, Bíró, T & Paus, R 2012, 'Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 3, pp. 978-986. https://doi.org/10.1210/jc.2011-1096
Knuever J, Poeggeler B, Gáspár E, Klinger M, Hellwig-Burgel T, Hardenbicker C et al. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis. Journal of Clinical Endocrinology and Metabolism. 2012 Mar 1;97(3):978-986. https://doi.org/10.1210/jc.2011-1096
Knuever, Jana ; Poeggeler, Burkhard ; Gáspár, Erzsébet ; Klinger, Matthias ; Hellwig-Burgel, Thomas ; Hardenbicker, Celine ; Tóth, Balázs I. ; Bíró, Tamás ; Paus, Ralf. / Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 3. pp. 978-986.
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