Thyroid-Stimulating Hormone, a Novel, Locally Produced Modulator of Human Epidermal Functions, Is Regulated by Thyrotropin-Releasing Hormone and Thyroid Hormones

Bodó, Enikő; Kany, Benedikt; Gáspár, Erzsébet; Knüver, Jana; Kromminga, Arno; Ramot, Yuval; Bı́ró, Tamás; Tiede, Stephan; Beek, Nina van; Pöeggeler, Burkhard; Meyer, Katja; Wenzel, B. E.; Paus, Ralf

doi:10.1210/jcem.95.3.9980

Cited by 18 publications

(41 citation statements)

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“…Because human skin is an extrapituitary site of TSH␤ expression (16,17) and is a newly recognized extrathyroidal target tissue of TSH activity (17,25), intracutaneously generated TSH may power human skin mitochondria in an auto-and/or paracrine manner. In fact, we have most recently shown that human epidermis expresses TSH␤ at the gene and protein level and that intraepidermal TSH expression is up-regulated by intracutaneously expressed TRH, but down-regulated by thyroid hormones (46), just as is characteristically seen within the central HPT axis (33). These findings added further credence to the hypothesis first proposed by Slominski, Tobin, and colleagues (16) that human skin may have established a peripheral equivalent of the central HPT axis.…”

Section: Discussionmentioning

confidence: 99%

Thyrotropin powers human mitochondria

Pöeggeler¹,

Knuever²,

Gáspár³

et al. 2010

FASEB j.

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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.

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Section: Discussionmentioning

confidence: 99%

Thyrotropin powers human mitochondria

Pöeggeler¹,

Knuever²,

Gáspár³

et al. 2010

FASEB j.

Self Cite

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show abstract

“…18 In IVL, we used human skin epithelium for positive and subcutaneous tissue for negative controls. 19 In the stained sections, cells with brown cytoplasm were regarded as ASC-positive. Three representative fields of each section (magnification Â60) were selected and captured by digital imaging.…”

Section: Studies In Clinical Samplesmentioning

confidence: 99%

Clinical significance of apoptosis-associated speck-like protein containing a caspase recruitment domain in oral squamous cell carcinoma

Shimane

Kobayashi

Takeoka³

et al. 2013

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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“…In addition, MKs are extremely sensitive to damage (e.g. by drugs, reactive oxygen species, radiation, inflammatory mediators, metabolic and hormonal abnormalities) and thus play a crucial role in multiple different hair loss disorders (Paus, 2006;Bodó et al, 2010). Therefore, we identify MKs as the optimal cell population to focus on when developing a simple mathematical model of HF cycling operating at the level of tissue dynamics.…”

Section: Identifying the Key Processes And Dynamical Changes In The Hmentioning

confidence: 99%