ANORECTIC EFFECTS OF ESTROGEN MAY BE MEDIATED BY DECREASED NEUROPEPTIDE-Y RELEASE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS
ANORECTIC EFFECTS OF ESTROGEN MAY BE MEDIATED BY DECREASED NEUROPEPTIDE-Y RELEASE IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS
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DOI：
10.1210/en.134.6.2367
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发表时间：
1994-06-01
期刊：
影响因子：
4.8
通讯作者：
KALRA, SP
中科院分区：
文献类型：
--
作者：
BONAVERA, JJ;DUBE, MG;KALRA, SP
有大量证据表明雌激素通过下丘脑的作用抑制食物摄入和体重增加。然而，介导雌激素的厌食作用的神经递质/神经调节剂尚不清楚。神经肽-Y (NPY) 是已知最有效的促食欲信号，下丘脑中产生 NPY 的神经元浓缩了 17 β-雌二醇 (E(2))。在这些研究中，我们测试了以下假设：雌激素诱导的厌食作用可能是由于先前与食物摄入控制有关的下丘脑部位 NPY 水平和释放的降低所致。结果表明，卵巢切除大鼠中不间断的 E(2) 生理水平抑制了每日食物摄入量和体重增加。对下丘脑五个部位的 NPY 浓度进行评估表明，E(2) 治疗大鼠的室旁核 (PVN) 和邻近的穹窿周核中的 NPY 水平选择性降低。相比之下，β-内啡肽（另一种效力较弱的促食欲肽）的浓度在任何下丘脑部位均不会被 E(2) 改变。在下一个实验中，在黑暗期开始时处死的大鼠中，研究了类似的E(2)处理对PVN和腹内侧核体外NPY释放的影响，此时食物摄入量随着PVN NPY分泌的增加而增加。结果表明，与对照大鼠相比，E(2)处理组的PVN的基础和KCl诱导的NPY释放显着减少。相比之下，Ep处理的大鼠的腹内侧核的基础和KCl诱导的NPY释放与对照大鼠相似。总的来说，这些结果表明雌激素抑制 NPY 水平并选择性地从 PVN 中释放。由于 PVN 中的 NPY 水平和释放已被证明与食欲状态高度相关，并且 PVN 是 NPY 作用的重要部位之一，这些发现意味着雌激素的厌食作用可能是通过 PVN NPY 神经支配的 NPY 释放减少来介导的。
There is a considerable body of evidence to suggest that estrogen suppresses food intake and body weight gain by an action in the hypothalamus. However, the neurotransmitter/neuromodulator mediating the anorectic effects of estrogen are unknown. Neuropeptide-Y (NPY) is the most potent orexigenic signal known, and NPY-producing neurons in the hypothalamus concentrate 17 beta-estradiol (E(2)) In these studies we tested the hypothesis that estrogen-induced anorectic effects may be due to decreased NPY levels and release in hypothalamic sites previously implicated in the control of food intake. The results show that uninterrupted physiological levels of E(2) in ovariectomized rats suppressed daily food intake and body weight gain. Evaluation of NPY concentrations in five hypothalamic sites showed that NPY levels were decreased selectively in the paraventricular nucleus (PVN) and neighboring perifornical nucleus of E(2)-treated rats. In contrast, concentrations of beta-endorphin, another less potent orexigenic peptide, were not changed by E(2) in any hypothalamic site. In the next experiment, the effects of similar E(2) treatment on NPY release in vitro from the PVN and ventromedial nucleus were studied in rats killed at the onset of the dark phase when food intake increases in conjunction with increased PVN NPY secretion. The results show that basal and KCl-induced NPY release were significantly decreased from the PVN of E(2)-treated compared to those in control rats. In contrast, both basal and KCl-induced NPY release from the ventromedial nucleus of Ep-treated rats were similar to those in control rats. Collectively, these results show that estrogen suppresses NPY levels and release selectively from the PVN. As NPY levels and release in the PVN have been shown to be highly correlated with appetite status, and the PVN is one of the important sites of NPY action, these findings imply that the anorectic effects of estrogen may be mediated by decreased NPY release from the PVN NPY innervations.