Regulation of Thyrotropin-Releasing Hormone-Expressing Neurons in Paraventricular Nucleus of the Hypothalamus by Signals of Adiposity

摘要

Masoud Ghamari-Langroudi, Kristen R. Vella, Dollada Srisai,Michelle L. Sugrue, Anthony N. Hollenberg, and Roger D. ConeFasting-induced suppression of thyroid hormone levels is anadaptiveresponsetoreduceenergyexpenditureinbothhumansand mice. This suppression is mediated by the hypothalamic-pituitary-thyroidaxisthroughareductioninTRHlevelsexpressedin neurons of the paraventricular nucleus of the hypothalamus(PVN). TRH gene expression is positively regulated by leptin.Whereas decreased leptin levels during fasting lead to a reduc-tion in TRH gene expression, the mechanisms underlying thisprocessarestillunclear.Indeed,evidenceexiststhatTRHneuronsin the PVN are targeted by leptin indirectly via the arcuate nu-cleus, whereas correlative evidence for a direct action exists aswell. Here we provide both in vivo and in vitro evidence that theactivity of hypothalamic-pituitary-thyroid axis is regulated byboth direct and indirect leptin regulation. We show that bothleptin and ? -MSH induce significant neuronal activity mediatedthroughapostsynapticmechanisminTRH-expressingneuronsofPVN. Furthermore, we provide in vivo evidence indicating thecontribution of each pathway in maintaining serum levels ofthyroid hormone.