title: Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes.
abstract: Thyroid 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.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, AB25 2ZD, United Kingdom.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Stoney
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen, Scotland, AB21 9SB, United Kingdom.
authors.forename: Gisela
authors.initials: G
authors.lastname: Helfer
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, AB25 2ZD, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Rodrigues
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Bucksburn, Aberdeen, Scotland, AB21 9SB, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Morgan
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, Scotland, AB25 2ZD, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: McCaffery
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D063928:Ependymoglial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013963:Thyroid Hormones / Q000494:pharmacology*; D014212:Tretinoin / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009478:Neuropeptide Y; C497930:Ppp1r1b protein, rat; D018168:Receptors, Retinoic Acid; D013963:Thyroid Hormones; D014746:Vimentin; D014212:Tretinoin; D011333:Pro-Opiomelanocortin; D000080924:Aldehyde Dehydrogenase 1 Family; C523119:Aldh1a1 protein, rat; D050697:Retinal Dehydrogenase
keywords: deiodinase; growth; retinoic acid receptor; thyroid hormone receptor; thyroid-stimulating hormone