PT  - JOURNAL ARTICLE
AU  - Csaba Fekete
AU  - Gábor Légrádi
AU  - Emese Mihály
AU  - Qin-Heng Huang
AU  - Jeffrey B. Tatro
AU  - William M. Rand
AU  - Charles H. Emerson
AU  - Ronald M. Lechan
TI  - 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
AID  - 10.1523/JNEUROSCI.20-04-01550.2000
DP  - 2000 Feb 15
TA  - The Journal of Neuroscience
PG  - 1550--1558
VI  - 20
IP  - 4
4099  - http://www.jneurosci.org/content/20/4/1550.short
4100  - http://www.jneurosci.org/content/20/4/1550.full
SO  - J. Neurosci.2000 Feb 15; 20
AB  - 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.