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PMID: 10662844 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

alpha-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.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 4 ·2000-02-15 ·Pages 1550-8

Fekete C, Légrádi G, Mihály E, Huang QH, Tatro JB, Rand WM, Emerson CH, Lechan RM

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 alpha-MSH antagonist activity, is contained in axon terminals that terminate on TRH neurons in the PVN, we raised the possibility that alpha-MSH may also participate in the mechanism by which leptin influences pro-TRH gene expression. By double-labeling immunocytochemistry, alpha-MSH-IR axon varicosities were juxtaposed to approximately 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 alpha-MSH-containing fibers also were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of alpha-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. alpha-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 alpha-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 alpha-MSH also contribute to the mechanism by which leptin administration restores thyroid hormone levels to normal in fasted animals.

MeSH Terms
Animals Body Weight/drug effects Fasting/physiology Gene Expression Regulation/drug effects,physiology Immunohistochemistry In Situ Hybridization Male Microscopy, Immunoelectron Nerve Endings/physiology,ultrastructure Neurons/cytology,physiology,ultrastructure Paraventricular Hypothalamic Nucleus/cytology,physiology,ultrastructure Protein Precursors/analysis,genetics Pyrrolidonecarboxylic Acid/analogs & derivatives Rats Rats, Sprague-Dawley Thyrotropin/blood Thyrotropin-Releasing Hormone/analysis,genetics Thyroxine/blood alpha-MSH/analysis,pharmacology,physiology
Chemicals
Protein Precursors alpha-MSH Thyrotropin-Releasing Hormone Thyrotropin pro-thyrotropin releasing hormone Thyroxine Pyrrolidonecarboxylic Acid
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fekete C
Tupper Research Institute, Department of Medicine, Division of Endocrinology, New England Medical Center, Boston, Massachusetts 02111, USA.
Légrádi G
Mihály E
Huang Q H
Tatro J B
Rand W M
Emerson C H
Lechan R M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
2000-02-15
Pages
1550-8
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772359
Subset
IM
Grants
NIDDK NIH HHS · R01 DK037021 · United States
NIDDK NIH HHS · R56 DK037021 · United States
NIDDK NIH HHS · DK-37021 · United States
External Links
PubMed source PMC Full Text View journal details
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