α-melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression

Csaba Fekete, Gábor Légrádi, Emese Mihály, Qin Heng Huang, Jeffrey B. Tatro, William M. Rand, Charles H. Emerson, Ronald M. Lechan

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

The hypothalamic arcuate nucleus has an essential role in mediating the homeostatic responses of the thyroid axis to fasting by altering the sensitivity of prothyrotropin-releasing hormone (pro-TRH) gene expression in the paraventricular nucleus (PVN) to feedback regulation by thyroid hormone. Because agouti-related protein (AGRP), a leptin-regulated, arcuate nucleus- derived peptide with α-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that α-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, α-MSH-IR axon varicosities were juxtaposed to ~70% of pro-TRH neurons in the anterior and periventricular parvocellular subdivisions of the PVN and to 34% of pro- TRH neurons in the medial parvocellular subdivision, establishing synaptic contacts both on the cell soma and dendrites. All pro-TRH neurons receiving contacts by α-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of α-MSH every 6 hr for 3 d prevented fasting-induced suppression of pro-TRH in the PVN but had no effect on AGRP mRNA in the arcuate nucleus. α-MSH also increased circulating levels of free thyroxine (T4) 2.5-fold over the levels in fasted controls, but free T4 did not reach the levels in fed controls. These data suggest that α-MSH has an important role in the activation of pro-TRH gene expression in hypophysiotropic neurons via either a mono- and/or multisynaptic pathway to the PVN, but factors in addition to α-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.

Original languageEnglish
Pages (from-to)1550-1558
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number4
Publication statusPublished - Feb 15 2000

Keywords

  • Agouti-related protein
  • Arcuate nucleus
  • Fasting
  • Leptin
  • Thyroid axis
  • Thyrotropin-releasing hormone
  • α-MSH

ASJC Scopus subject areas

  • Neuroscience(all)

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