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1.

001-es BibID:BIBFORM016014
Első szerző:Bodó Enikő
Cím:Thyroid-Stimulating Hormone, a Novel, Locally Produced Modulator of Human Epidermal Functions, Is Regulated by Thyrotropin-Releasing Hormone and Thyroid Hormones / Bodo, E., Kany, B., Gaspar, E., Knuver, J., Kromminga, A., Ramot, Y., Biro, T., Tiede, S., van Beek, N., Poeggeler, B., Meyer, K. C., Wenzel, B. E., Paus, R.
Dátum:2010
ISSN:0013-7227
Megjegyzések:Several elements of the hypothalamic-pituitary-thyroid axis (HPT) reportedly are transcribed by human skin cell populations, and human hair follicles express functional receptors for TSH. Therefore, we asked whether the epidermis of normal human skin is yet another extrathyroidal target of TSH and whether epidermis even produces TSH. If so, we wanted to clarify whether intraepidermal TSH expression is regulated by TRH and/or thyroid hormones and whether TSH alters selected functions of normal human epidermis in situ. TSH and TSH receptor (TSH-R) expression were analyzed in the epidermis of normal human scalp skin by immunohistochemistry and PCR. In addition, full-thickness scalp skin was organ cultured and treated with TSH, TRH, or thyroid hormones, and the effect of TSH treatment on the expression of selected genes was measured by quantitative PCR and/or quantitative immunohistochemistry. Here we show that normal human epidermis expresses TSH at the mRNA and protein levels in situ and transcribes TSH-R. It also contains thyrostimulin transcripts. Intraepidermal TSH immunoreactivity is up-regulated by TRH and down-regulated by thyroid hormones. Although TSH-R immunoreactivity in situ could not be documented within the epidermis, but in the immediately adjacent dermis, TSH treatment of organ-cultured human skin strongly up-regulated epidermal expression of involucrin, loricrin, and keratins 5 and 14. Thus, normal human epidermis in situ is both an extrapituitary source and (possibly an indirect) target of TSH signaling, which regulates defined epidermal parameters. Intraepidermal TSH expression appears to be regulated by the classical endocrine controls that determine the systemic HPT axis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Endocrinology. - 151 : 4 (2010), p. 1633-1642. -
További szerzők:Kany Benedikt Gáspár Erzsébet Knüver, Jana Kromminga, Arno Ramot, Yuval Bíró Tamás (1968-) (élettanász) Tiede, Stephan van Beek, Nina Poeggeler, Burkhard Meyer, Katja C. Wenzel, Björn E. Paus, Ralf
Internet cím:DOI
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2.

001-es BibID:BIBFORM033987
Első szerző:Knüver, Jana
Cím:Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis / Knuever J., Poeggeler B., Gáspár E., Klinger M., Hellwig-Burgel T., Hardenbicker C., Tóth B. I., Bíró T., Paus R.
Dátum:2012
ISSN:0021-972X
Megjegyzések: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-1 alpha). 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. (J Clin Endocrinol Metab 97: 978-986, 2012)
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Clinical Endocrinology & Metabolism 97 : 3 (2012), p. 978-986. -
További szerzők:Poeggeler, Burkhard Gáspár E. Klinger, Matthias Hellwig-Burgel, T. Hardenbicker, Celine Tóth István Balázs (1978-) (élettanász) Bíró Tamás (1968-) (élettanász) Paus, Ralf
Internet cím:DOI
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3.

001-es BibID:BIBFORM016011
Első szerző:Langan, Ewan A.
Cím:Thyrotropin-releasing hormone and oestrogen differentially regulate prolactin and prolactin receptor expression in female human skin and hair follicles in vitro / Langan, E. A., Ramot, Y., Hanning, A., Poeggeler, B., Biro, T., Gaspar, E., Funk, W., Griffiths, C. E. M., Paus, R.
Dátum:2010
ISSN:0007-0963
Megjegyzések:Human skin and scalp hair follicles are both a nonclassical target and an extrapituitary source of prolactin (PRL), which is a potent hair growth modulator. However, how the expression of PRL and PRL receptor (PRLR) is regulated in human skin is unknown. Objectives To investigate whether two key stimulators of pituitary PRL secretion, thyrotropin-releasing hormone (TRH) and oestrogen, also regulate cutaneous PRL and PRLR expression. Methods Female scalp skin and/or microdissected hair follicles were treated for 6 days in serum-free organ culture with oestrogen (100 nmol L-1), TRH (1-10 ng mL-1, 3-30 nm) or vehicle control. Quantitative immunohistomorphometry of skin and hair follicle sections was complemented with quantitative polymerase chain reaction for PRL and PRLR in cultured hair follicles and/or female human outer root sheath (ORS) keratinocytes. Results Oestrogen treatment significantly upregulated PRL and PRLR immunoreactivity in selected skin and hair follicle compartments, at the gene and protein level (P < 0 center dot 05). TRH significantly increased PRL immunoreactivity and transcription in hair follicles (P < 0 center dot 05); however, while it also increased PRLR transcription in hair follicles, it downregulated PRLR immunoreactivity in the hair follicle ORS (P < 0 center dot 05). Conclusions Our pilot study shows that two key endocrine controls of pituitary PRL secretion, oestrogen and TRH, also regulate PRL and PRLR expression in human skin. This provides novel insights into the regulation of extrapituitary PRL and PRLR expression, and invites exploration of oestrogen and TRH as novel therapeutic agents in the management of skin and hair diseases characterized by aberrant PRLR-mediated signalling.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:British Journal of Dermatology. - 162 : 5 (2010), p. 1127-1131. -
További szerzők:Ramot, Yuval Hanning, A. Poeggeler, Burkhard Bíró Tamás (1968-) (élettanász) Gáspár E. Funk, W. Griffiths, Christopher E. M. Paus, Ralf
Internet cím:DOI
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4.

001-es BibID:BIBFORM016018
Első szerző:Poeggeler, Burkhard
Cím:Thyrotropin powers human mitochondria / Poeggeler, B., Knuever, J., Gaspar, E., Biro, T., Klinger, M., Bodo, E., Wiesner, R. J., Wenzel, B. E., Paus, R.
Dátum:2010
ISSN:0892-6638
Megjegyzések: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 cytochromec-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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The FASEB Journal. - 24 : 5 (2010), p. 1525-1531. -
További szerzők:Knüver, Jana Gáspár Erzsébet Bíró Tamás (1968-) (élettanász) Klinger, Matthias Bodó Enikő Wiesner, Rudolf J. Wenzel, Björn E. Paus, Ralf
Internet cím:DOI
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5.

001-es BibID:BIBFORM048833
035-os BibID:PMID:23949722
Első szerző:Vidali, Silvia
Cím:Hypothalamic-Pituitary-Thyroid Axis Hormones Stimulate Mitochondrial Function and Biogenesis in Human Hair Follicles / Silvia Vidali, Jana Knuever, Johannes Lerchner, Melanie Giesen, Tamás Bíró, Matthias Klinger, Barbara Kofler, Wolfgang Funk, Burkhard Poeggeler, Ralf Paus
Dátum:2014
ISSN:0022-202X
Megjegyzések:Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30?nM), TSH (10?mU?ml-1), thyroxine (T4) (100?nM), and triiodothyronine (T3) (100?pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Calcium (Ca2+) signalling
Ion channel
Membrane transport
Molecular mechanisms of disease
Skin
TRP channels
Megjelenés:Journal of Investigative Dermatology. - 134 (2014), p. 33-42. -
További szerzők:Knüver, Jana Lerchner, Johannes Giesen, Melanie Bíró Tamás (1968-) (élettanász) Klinger, Matthias Kofler, Barbara Funk, Wolfgang Poeggeler, Burkhard Paus, Ralf
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