title: Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.
abstract: How Retinoid X receptors (RXR) and thyroid hormone receptors (TR) interact on negative TREs and whether RXR subtype specificity is determinant in such regulations is unknown. In a set of functional studies, we analyzed RXR subtype effects in T3-dependent repression of hypothalamic thyrotropin-releasing hormone (Trh). Two-hybrid screening of a hypothalamic paraventricular nucleus cDNA bank revealed specific, T3-dependent interaction of TRs with RXRβ. In vivo chromatin immuno-precipitation showed recruitment of RXRs to the TRE-site 4 region of the Trh promoter in the absence of T3. In vivo overexpression of RXRα in the mouse hypothalamus heightened T3-independent Trh transcription, whereas RXRβ overexpression abrogated this activity. Loss of function of RXRα and β by shRNAs induced inverse regulations. Thus, RXRα and RXRβ display specific roles in modulating T3-dependent regulation of Trh. These results provide insight into the actions of these different TR heterodimerization partners within the context of a negatively regulated gene.
authors.affiliation: CNRS UMR 7221-USM 501, «Evolution of Endocrine Regulations», «Regulations, Development and Molecular Diversity» Department, Muséum National d'Histoire Naturelle, 57 rue Cuvier, CP 32, 75231 Paris Cedex 5, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Decherf
authors.forename: Isabelle
authors.initials: I
authors.lastname: Seugnet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Becker
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Demeneix
authors.forename: Marie-Stéphanie
authors.initials: MS
authors.lastname: Clerget-Froidevaux
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D011401:Promoter Regions, Genetic; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism*; D049230:Retinoid X Receptor beta / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000502:physiology
chemical_list: D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone
keywords: Negative regulation; Paraventricular nucleus of hypothalamus (PVN); Repression; Retinoid X receptor (RXR); Thyroid hormone (T(3)); Thyrotropin-releasing hormone (TRH)