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The Journal of Neuroscience, July 15, 2002, 22(14):6265-6271
Leptin Regulates Growth Hormone-Releasing Factor, Somatostatin,
and  -Melanocyte-Stimulating Hormone But Not Neuropeptide Y Release
in Rat Hypothalamus In Vivo: Relation with Growth Hormone
Secretion
Hajime
Watanobe1 and
Satoshi
Habu2
1 Division of Internal Medicine, Clinical Research
Center, International University of Health and Welfare, Otawara,
Tochigi 324-8501, Japan, and 2 Division of Endocrinology,
Diabetology, and Metabolism, Department of Medicine, Aichi Medical
University School of Medicine, Nagakute, Aichi 480-1195, Japan
It is known that leptin, an adipocyte-derived hormone, exerts a
stimulatory effect on growth hormone (GH) secretion in various animal
species. However, no previous study examined in vivo
whether leptin affects the secretion of GH-releasing factor (GRF),
somatostatin (SRIH), and some other closely relevant neurohormones in
the hypothalamus. Therefore, in this study we investigated the effects
of direct leptin infusion into the hypothalamus on the in
vivo release of GRF, SRIH,  -melanocyte-stimulating hormone
(-MSH), and neuropeptide Y (NPY) in freely moving adult male rats
using the push-pull perfusion. Leptin was infused into the median
eminence-arcuate nucleus complex at three different concentrations,
i.e., 1.0 (normal feeding level), 3.0, and 10 ng/ml (mild obesity
level). In normally fed rats, only 10 ng/ml leptin was able to
stimulate GH secretion, whereas in 3 d fasted rats, GH release was
dose-dependently stimulated by 1.0 and 3.0 ng/ml leptin, although its
10 ng/ml dose did not produce additional effects. The facilitation of
GH secretion occurred as increased pulse amplitudes without significant
changes in the pulse frequency. During the leptin infusion, the
hypothalamic GRF increased and SRIH decreased in magnitudes that
approximately paralleled those of GH changes. Leptin stimulated the
release of -MSH in the fasted but not fed rats. It is likely that
the fasting-induced increase in the hypothalamic -MSH sensitivity to
leptin is relevant to ingestive behavior involving leptin. Leptin was
without effect on NPY release in either the fed or fasted group.
Although it is certain that NPY mediates at least part of the metabolic
actions of leptin, NPY is unlikely to be involved in the acute effects
of leptin on GH, GRF, and SRIH secretion. These results demonstrate for
the first time that leptin can alter the in vivo release
of both GRF and SRIH in rat hypothalamus concurrently with the
stimulation of GH secretion.
Key words:
leptin; growth hormone; growth hormone-releasing factor; somatostatin; -melanocyte-stimulating hormone; neuropeptide Y; arcuate nucleus; median eminence; push-pull perfusion
Copyright © 2002 Society for Neuroscience 0270-6474/02/22146265-07$05.00/0
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