Peroxisome proliferator-activated receptor-gamma (PPARgamma) modulates hypothalamic Trh regulation in vivo

Mol Cell Endocrinol. 2010 Apr 12;317(1-2):44-52. doi: 10.1016/j.mce.2009.11.001. Epub 2009 Nov 10.


Thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor gamma (PPARgamma) co-regulate numerous peripheral metabolic responses. To examine potential crosstalk between PPARgamma and TRbeta in the hypothalamus, thyrotropin-releasing hormone (Trh) regulation in the newborn mouse hypothalamus was followed. QPCR showed PPARgamma to be expressed in the hypothalamus at this developmental stage. Intracerebral injection of PPARgamma agonists modified transcription from a TRH-luc construct introduced into the hypothalamus and increased serum thyroxine levels. Furthermore, shRNA-based in vivo PPARgamma knockdown amplified T(3)-independent transcription and PPARgamma overexpression dose-dependently abrogated T(3)-dependent Trh repression. Overexpression of retinoid X receptor-alpha (RXRalpha), the common heterodimeric partner of PPARgamma and TRbeta, rescued PPARgamma abrogation of T(3)-dependent repression. Thus, competition for RXR could represent one mechanism underlying this hypothalamic crosstalk between PPARgamma and TRbeta. These demonstrations of PPARgamma effects on hypothalamic Trh transcription in vivo consolidate the role of the TRH neuron as a central integrator of energy homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Animals
  • Animals, Newborn
  • Gene Expression Regulation* / drug effects
  • Gene Knockdown Techniques
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Injections, Intraventricular
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Pioglitazone
  • Promoter Regions, Genetic / genetics
  • Retinoid X Receptor alpha / metabolism
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology
  • Thyroid Hormone Receptors beta / metabolism
  • Thyrotropin-Releasing Hormone / genetics*
  • Thyrotropin-Releasing Hormone / metabolism
  • Thyroxine / metabolism
  • Transfection
  • Triiodothyronine / pharmacology


  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Glucose Transporter Type 4
  • PPAR gamma
  • Retinoid X Receptor alpha
  • Slc2a4 protein, mouse
  • Thiazolidinediones
  • Thyroid Hormone Receptors beta
  • Rosiglitazone
  • Triiodothyronine
  • Thyrotropin-Releasing Hormone
  • Thyroxine
  • Pioglitazone