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Mol Cell Endocrinol. 2013 Dec 5;381(1-2):115-23. doi: 10.1016/j.mce.2013.07.016. Epub 2013 Jul 26.

Retinoic X receptor subtypes exert differential effects on the regulation of Trh transcription.

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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.


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.


Negative regulation; Paraventricular nucleus of hypothalamus (PVN); Repression; Retinoid X receptor (RXR); Thyroid hormone (T(3)); Thyrotropin-releasing hormone (TRH)

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