Peroxisome proliferator-activated receptor-γ (PPARγ) modulates hypothalamic Trh regulation in vivo

Thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor gamma (PPAR gamma) co-regulate numerous peripheral metabolic responses. To examine potential crosstalk between PPAR gamma and TR beta in the hypothalamus, thyrotropin-releasing hormone (Trh) regulation in the newborn mouse hypothalamus was followed. QPCR showed PPAR gamma to be expressed in the hypothalamus at this developmental stage. Intracerebral injection of PPAR gamma agonists modified transcription from a TRH-luc construct introduced into the hypothalamus and increased serum thyroxine levels. Furthermore shRNA-based in vivo, PPAR gamma knockdown amplified T-3-independent transcription and PPAR gamma over expression dose-dependently abrogated T-3-dependent Trh repression. Overexpression of retinoid X receptor-alpha (RXR alpha), the common heterodimeric partner of PPAR gamma and TR beta, rescued PPAR gamma abrogation of T-3-dependent repression. Thus, competition for RXR could represent one mechanism underlying this hypothalamic crosstalk between PPAR gamma and TR beta. These demonstrations of PPAR gamma effects on hypothalamic Trh transcription in vivo consolidate the role of the TRH neuron as a central integrator of energy homeostasis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.