Seal L J, Small C J, Dhillo W S, Stanley S A, Abbott C R, Ghatei M A, Bloom S R
Department of Metabolic Medicine, Imperial College School of Medicine, London, United Kingdom W12 0NN.
Endocrinology. 2001 Oct;142(10):4236-43. doi: 10.1210/endo.142.10.8419.
PRL-releasing peptide inhibits food intake after intracerebroventricular injection. PRL-releasing peptide immunoreactivity is found in several hypothalamic nuclei involved in feeding, with highest levels in the paraventricular and dorsomedial hypothalamic nuclei. The aim of this study was to examine the effect of PRL-releasing peptide on food intake after administration into these nuclei. Paraventricular nucleus injection of PRL-releasing peptide did not alter food intake. Dorsomedial hypothalamic nucleus injection of PRL-releasing peptide decreased 1 h food intake [PRL-releasing peptide (1 nmol) 83.4 +/- 6.1% saline all; P < 0.05]; and continued until 8 h postinjection [PRL-releasing peptide (1 nmol) 89.2 +/- 4.1% saline; P < 0.05]. To investigate the mechanism of this inhibition of food intake, we examined PRL-releasing peptide's effect on neuropeptide release from hypothalamic explants. alpha MSH release was increased [PRL-releasing peptide (100 nmol), 5.4 +/- 1.6 pmol/explant; change vs. basal, P < 0.01], whereas agouti-related protein release was unchanged. The release of cocaine- and amphetamine-regulated transcript was inhibited [PRL-releasing peptide (100 nmol), -33.5 +/- 12.6 pmol/explant; change vs. basal, P < 0.01]. PRL-releasing peptide dose-dependently increased neurotensin release [PRL-releasing peptide (1 nmol), 3.7 +/- 2.6 pmol/explant; change vs. basal, P = NS; PRL-releasing peptide (10 nmol), 7.2 +/- 2.7 pmol/explant; change vs. basal, P < 0.01; PRL-releasing peptide (100 nmol), 36.8 +/- 5.4 pmol/explant; change vs. basal, P < 0.001]. Our data suggest that the dorsomedial hypothalamic nucleus is important in the inhibitory effect of PRL-releasing peptide on food intake and that PRL-releasing peptide alters the release of several hypothalamic neuropeptides important in the control of food intake.
催乳素释放肽经脑室内注射后可抑制食物摄入。在几个参与进食调节的下丘脑核团中发现了催乳素释放肽免疫反应性，其中室旁核和下丘脑背内侧核中的水平最高。本研究的目的是研究将催乳素释放肽注入这些核团后对食物摄入的影响。向室旁核注射催乳素释放肽不会改变食物摄入量。向下丘脑背内侧核注射催乳素释放肽可减少1小时的食物摄入量[催乳素释放肽（1纳摩尔），与生理盐水组相比为83.4±6.1%；P<0.05]；这种减少持续至注射后8小时[催乳素释放肽（1纳摩尔），与生理盐水组相比为89.2±4.1%；P<0.05]。为了研究这种食物摄入抑制作用的机制，我们检测了催乳素释放肽对下丘脑外植体神经肽释放的影响。α-促黑素（αMSH）的释放增加[催乳素释放肽（100纳摩尔），5.4±1.6皮摩尔/外植体；与基础值相比的变化，P<0.01]，而刺鼠相关蛋白的释放未改变。可卡因和苯丙胺调节转录物的释放受到抑制[催乳素释放肽（100纳摩尔），-33.5±12.6皮摩尔/外植体；与基础值相比的变化，P<0.01]。催乳素释放肽剂量依赖性地增加神经降压素的释放[催乳素释放肽（1纳摩尔），3.7±2.6皮摩尔/外植体；与基础值相比的变化，P=无显著性差异；催乳素释放肽（10纳摩尔），7.2±2.7皮摩尔/外植体；与基础值相比的变化，P<0.01；催乳素释放肽（100纳摩尔），36.8±5.4皮摩尔/外植体；与基础值相比的变化，P<0.001]。我们的数据表明，下丘脑背内侧核在催乳素释放肽对食物摄入的抑制作用中起重要作用，且催乳素释放肽可改变几种对食物摄入控制至关重要的下丘脑神经肽的释放。
