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dc.contributor.authorStoney, P.N.*
dc.contributor.authorHelfer, Gisela*
dc.contributor.authorRodrigues, D.*
dc.contributor.authorMorgan, P.J.*
dc.contributor.authorMcCaffery, P.J.*
dc.date.accessioned2016-11-28T15:25:46Z
dc.date.available2016-11-28T15:25:46Z
dc.date.issued2016-03
dc.identifier.citationStoney PN, Helfer G, Morgan PJ and McCaffery PJ (2016) Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes. Glia. 64(3): 425-439.
dc.identifier.urihttp://hdl.handle.net/10454/10838
dc.descriptionYes
dc.description.abstractThyroid hormone (TH) is essential for adult brain function and its actions include several key roles in the hypothalamus. Although TH controls gene expression via specific TH receptors of the nuclear receptor class, surprisingly few genes have been demonstrated to be directly regulated by TH in the hypothalamus, or the adult brain as a whole. This study explored the rapid induction by TH of retinaldehyde dehydrogenase 1 (Raldh1), encoding a retinoic acid (RA)-synthesizing enzyme, as a gene specifically expressed in hypothalamic tanycytes, cells that mediate a number of actions of TH in the hypothalamus. The resulting increase in RA may then regulate gene expression via the RA receptors, also of the nuclear receptor class. In vivo exposure of the rat to TH led to a significant and rapid increase in hypothalamic Raldh1 within 4 hours. That this may lead to an in vivo increase in RA is suggested by the later induction by TH of the RA-responsive gene Cyp26b1. To explore the actions of RA in the hypothalamus as a potential mediator of TH control of gene regulation, an ex vivo hypothalamic rat slice culture method was developed in which the Raldh1-expressing tanycytes were maintained. These slice cultures confirmed that TH did not act on genes regulating energy balance but could induce Raldh1. RA has the potential to upregulate expression of genes involved in growth and appetite, Ghrh and Agrp. This regulation is acutely sensitive to epigenetic changes, as has been shown for TH action in vivo. These results indicate that sequential triggering of two nuclear receptor signalling systems has the capability to mediate some of the functions of TH in the hypothalamus.
dc.language.isoen
dc.rights© 2016 The Authors. Glia Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,provided the original work is properly cited.
dc.subjectThyroid hormone receptor
dc.subjectThyroid-stimulating hormone
dc.subjectDeiodinase
dc.subjectRetinoic acid receptor
dc.subjectGrowth
dc.titleThyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes
dc.status.refereedYes
dc.date.Accepted2015-10-12
dc.date.application2015-11-03
dc.typeArticle
dc.type.versionPublished version
dc.identifier.doihttps://doi.org/10.1002/glia.22938
dc.rights.licenseCC-BY
refterms.dateFOA2018-07-27T02:08:47Z
dc.openaccess.statusopenAccess


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