title: Thyrotropin powers human mitochondria.
abstract: Here we demonstrate that the neuropeptide hormone thyrotropin (TSH), which controls thyroid hormone production, exerts a major nonclassical function in mitochondrial biology. Based on transcriptional, ultrastructural, immunohistochemical, and biochemical evidence, TSH up-regulates mitochondrial biogenesis and consequently activity in organ-cultured normal human epidermis in situ. Mitochondrial activity was assessed by measuring 2 key components of the respiratory chain. The abundance of mitochondria was assessed employing 2 independent morphological techniques: counting their numbers in human epidermis by high-magnification light microscopy of skin sections immunostained for mitochondria-selective cytochrome-c-oxidase subunit 1 (MTCO1) and transmission electron microscopy (TEM). Treatment with 10 mU/ml of TSH for 6 d strongly up-regulates the number of light-microscopically visualized, MTCO1-demarcated mitochondria. On the ultrastructural level, TEM confirms that TSH indeed stimulates mitochondrial proliferation and biogenesis in the perinuclear region of human skin epidermal keratinocytes. On the transcriptional level, TSH up-regulates MTCO1 mRNA (quantitative RT-PCR) and significantly enhances complex I and IV (cytochrome-c-oxidase) activity. This study pioneers the concept that mitochondrial energy metabolism and biogenesis in a normal, prototypic human epithelial tissue underlies potent neuroendocrine controls and introduces human skin organ culture as a clinically relevant tool for further exploring this novel research frontier in the control of mitochondrial biology.
authors.affiliation: Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeggeler
authors.forename: Jana
authors.initials: J
authors.lastname: Knuever
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Gáspár
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Matthias
authors.initials: M
authors.lastname: Klinger
authors.forename: Eniko
authors.initials: E
authors.lastname: Bodó
authors.forename: Rudolf J
authors.initials: RJ
authors.lastname: Wiesner
authors.forename: Björn E
authors.initials: BE
authors.lastname: Wenzel
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D002478:Cells, Cultured; D004734:Energy Metabolism; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D013972:Thyrotropin