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, E. Mihály, Qin Heng Huang, Jeffrey B. Tatro, William M. Rand, Charles H. Emerson, Ronald M. Lechan

Research output: Article

225 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 - febr. 15 2000

Fingerprint

Melanocyte-Stimulating Hormones
Thyrotropin-Releasing Hormone
Paraventricular Hypothalamic Nucleus
Fasting
Hormones
Gene Expression
Neurons
Agouti-Related Protein
Arcuate Nucleus of Hypothalamus
Leptin
Thyroid Hormones
Axons
Intraventricular Infusions
Presynaptic Terminals
Carisoprodol
Dendrites
Thyroxine
Thyroid Gland
Immunohistochemistry
Messenger RNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{63e68d746f6f42a4b4ea13eb3126530f,
title = "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",
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.",
keywords = "α-MSH, Agouti-related protein, Arcuate nucleus, Fasting, Leptin, Thyroid axis, Thyrotropin-releasing hormone",
author = "Csaba Fekete and G{\'a}bor L{\'e}gr{\'a}di and E. Mih{\'a}ly and Huang, {Qin Heng} and Tatro, {Jeffrey B.} and Rand, {William M.} and Emerson, {Charles H.} and Lechan, {Ronald M.}",
year = "2000",
month = "2",
day = "15",
language = "English",
volume = "20",
pages = "1550--1558",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "4",

}

TY - JOUR

T1 - 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

AU - Fekete, Csaba

AU - Légrádi, Gábor

AU - Mihály, E.

AU - Huang, Qin Heng

AU - Tatro, Jeffrey B.

AU - Rand, William M.

AU - Emerson, Charles H.

AU - Lechan, Ronald M.

PY - 2000/2/15

Y1 - 2000/2/15

N2 - 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.

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.

KW - α-MSH

KW - Agouti-related protein

KW - Arcuate nucleus

KW - Fasting

KW - Leptin

KW - Thyroid axis

KW - Thyrotropin-releasing hormone

UR - http://www.scopus.com/inward/record.url?scp=0342858793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0342858793&partnerID=8YFLogxK

M3 - Article

C2 - 10662844

AN - SCOPUS:0342858793

VL - 20

SP - 1550

EP - 1558

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 4

ER -