Leptin regulates growth hormone-releasing factor, somatostatin, and alpha-melanocyte-stimulating hormone but not neuropeptide Y release in rat hypothalamus in vivo: relation with growth hormone secretion.
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, alpha-melanocyte-stimulating hormone (alpha-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 alpha-MSH in the fasted but not fed rats. It is likely that the fasting-induced increase in the hypothalamic alpha-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.
Division of Internal Medicine, Clinical Research Center, International University of Health and Welfare, Otawara, Tochigi 324-8501, Japan. watah@iuhw.ac.jp
Hajime
H
Watanobe
Satoshi
S
Habu
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D008845:Microinjections; D009478:Neuropeptide Y / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism*
D020738:Leptin; D009478:Neuropeptide Y; D013004:Somatostatin; D000521:alpha-MSH; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone