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The Journal of Neuroscience, February 15, 2000, 20(4):1550-1558
-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
Fekete1, 2,
Gábor
Légrádi1,
Emese
Mihály1,
Qin-Heng
Huang1,
Jeffrey B.
Tatro1,
William M.
Rand3,
Charles H.
Emerson4, and
Ronald M.
Lechan1, 5
1 Tupper Research Institute and Department of Medicine,
Division of Endocrinology, Diabetes, Metabolism, and Molecular
Medicine, New England Medical Center, Boston, Massachusetts 02111, 2 Department of Neurobiology, Institute of Experimental
Medicine, Hungarian Academy of Sciences, Budapest, Hungary,
3 Department of Community Health, Tufts University School
of Medicine, Boston, Massachusetts 02111, 4 Department of
Medicine, Division of Endocrinology, University of Massachusetts
Medical School, Worcester, Massachusetts 01655, and
5 Department of Neuroscience, Tufts University School of
Medicine, Boston, Massachusetts 02111
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 -MSH
antagonist activity, is contained in axon terminals that terminate on
TRH neurons in the PVN, we raised the possibility that -MSH may also
participate in the mechanism by which leptin influences pro-TRH gene
expression. By double-labeling immunocytochemistry, -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 -MSH-containing fibers also
were innervated by axons containing AGRP. The intracerebroventricular infusion of 300 ng of -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. -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 -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
-MSH also contribute to the mechanism by which leptin administration
restores thyroid hormone levels to normal in fasted animals.
Key words:
thyrotropin-releasing hormone; thyroid axis; -MSH; arcuate nucleus; fasting; agouti-related protein; leptin
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041550-09$05.00/0
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E. A. Nillni, C. Vaslet, M. Harris, A. Hollenberg, C. Bjorbak, and J. S. Flier
Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis. EVIDENCE FOR DIRECT AND INDIRECT PATHWAYS
J. Biol. Chem.,
November 10, 2000;
275(46):
36124 - 36133.
[Abstract]
[Full Text]
[PDF]
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