The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion.

The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion.
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腹侧前核核与禁食诱导的瘦素水平的变化和协调的黄体激素分泌联系起来。

DOI:
10.1523/jneurosci.0405-09.2009
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发表时间:
2009-04-22
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Elias CF
Elias CF
中科院分区:
其他
文献类型:
--
作者:
Donato J Jr;Silva RJ;Sita LV;Lee S;Lee C;Lacchini S;Bittencourt JC;Franci CR;Canteras NS;Elias CF

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低瘦素水平的生理条件,如在负能量平衡期间观察到的那些,通常以抑制促黄体生成激素(LH)分泌和生育为特征。给予瘦素可恢复LH水平和生殖功能。瘦素对LH分泌的作用被认为是由大脑介导的。然而,介导这种效应的神经元群体仍然不确定。下丘脑腹侧乳头体前核(PMV)神经元表达密集浓度的瘦素受体,并投射到与生殖控制相关的脑区。因此,我们假设PMV位于很好的位置,以介导瘦素对LH分泌的作用。为了验证我们的假设,我们进行了双侧兴奋性毒性病变的成年雌性大鼠的PMV。PMV损伤的动物表现出明显的发情周期中断,保持在乏情期15至20天。明显恢复后的周期性,动物灌注在下午的动情前期表现出下降的Fos免疫反应性的前腹侧室周核和促性腺激素释放激素神经元。PMV损伤的动物也表现出减少雌激素和LH分泌的发情前期。术后7周,病变未引起平均摄食量和体重变化。我们进一步测试了瘦素在PMV损伤的禁食动物中诱导LH分泌的能力。我们发现PMV的完全病变排除了空腹时LH分泌的瘦素刺激。我们的研究结果表明,PMV是一个关键网站连接瘦素水平的变化和协调控制的生殖。
Physiological conditions of low leptin levels like those observed during negative energy balance are usually characterized by the suppression of luteinizing hormone (LH) secretion and fertility. Leptin administration restores LH levels and reproductive function. Leptin action on LH secretion is thought to be mediated by the brain. However, the neuronal population that mediates this effect is still undefined. The hypothalamic ventral premammillary nucleus (PMV) neurons express a dense concentration of leptin receptors and project to brain areas related to reproductive control. Therefore, we hypothesized that the PMV is well located to mediate leptin action on LH secretion. To test our hypothesis, we performed bilateral excitotoxic lesions of the PMV in adult female rats. PMV-lesioned animals displayed a clear disruption of the estrous cycle, remaining in anestrus for 15 to 20 days. After apparent recovery of cyclicity, animals perfused in the afternoon of proestrus showed decreased Fos immunoreactivity in the anteroventral periventricular nucleus and in gonadotropin releasing hormone neurons. PMV-lesioned animals also displayed decreased estrogen and LH secretion on proestrus. Lesions caused no changes in mean food intake and body weight up to 7 weeks after surgery. We further tested the ability of leptin to induce LH secretion in PMV-lesioned fasted animals. We found that complete lesions of the PMV precluded leptin stimulation of LH secretion on fasting. Our findings demonstrate that the PMV is a key site linking changing levels of leptin and coordinated control of reproduction.