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Thyrotropin receptor signalling links skin and thyroid disease

Thyroid dysfunction is frequently associated with skin and hair diseases; however, the underlying pathogenic mechanisms are poorly understood. Pathological activation of the thyroid stimulating hormone receptor (TSHR) is the key feature of both hyper- and hypo-thyrodism. Expression of the (TSHR) has been reported in several extra-thyroidal locations including adipose tissue, bone and skin fibroblasts. TSHR expression may explain the association between the thyroid and skin disease. The TSHR can also be activated by a newly discovered glycoprotein hormone, known as thyrostimulin. This hormone is composed of a dimer of unique α 2 and β 5 subunits. Although thyrostimulin has not been detected in the circulation. However, both subunits have been shown to be expressed in different tissues including the skin. The aim of this study is to examine the expression of the TSHR and thyrostimulin in the skin. In addition, to investigate the expression of a variant form of the TSHR in human and mouse skin and, other mouse tissues. RT-PCR using primers specific for the full length receptor and the truncated variant revealed that although the variant was widely expressed in mouse tissues including skin, it was not found in human skin. The full length receptor and thyrostimulin were found to be co-expressed in eye, testis and skin. Immunohistochemistry of frozen skin and thyroid sections using commercially available antibodies against the extracellular (A9) and transmembrane domains (A7) of TSHR demonstrates that TSHR is not expressed in the epidermis but expressed in dermal fibroblasts and in myoepithelium around sweat glands. A new β5 antibody was characterised by western blotting and immunohistochemistry for future investigation of β5 expression in the skin. These data suggest a functional role for TSHR signalling possibly via thyrostimulin in the skin and that the variant form,although potentially present in some tissues, is unlikely to be important in human skin.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:569924
Date January 2012
CreatorsEl Mansori, Ibtessam Mustafa
PublisherCardiff University
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://orca.cf.ac.uk/46110/

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