Altered expression of Agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation
Altered expression of Agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation
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DOI：
10.1210/en.140.6.2645
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发表时间：
1999-06-01
期刊：
影响因子：
4.8
通讯作者：
Smith, MS
中科院分区：
文献类型：
--
作者：
Chen, PL;Li, CE;Smith, MS
在哺乳期间，神经肽 Y (NPY) 的水平在介导食物摄入中起重要作用，在包括弓状核 (ARH) 在内的许多下丘脑区域显着升高。为了确定可能对调节哺乳期间食物摄入量增加和能量稳态改变起重要作用的其他下丘脑系统，本研究检测了刺豚鼠相关蛋白（AGRP）的表达，这是最近描述的皮肤刺豚鼠蛋白的同源物。 AGRP 存在于下丘脑中，并被认为在食物摄入的调节中发挥重要作用。在第一个实验中，动物在发情周期的发情间期（雌激素水平处于基础水平且与哺乳期相似的周期阶段）或产后第 12-13 天进行了研究。哺乳期动物在产后第二天将其窝数调整为八只幼崽。脑组织切片用于通过原位杂交测量 AGRP 信使 RNA (mRNA) 水平。 AGRP mRNA 信号主要存在于 ARH 的腹内侧部分，该部分已被证明含有高密度的 NPY 神经元。与绝情雌性相比，在哺乳动物 ARH 的中尾部分观察到 AGRP mRNA 含量显着增加。 ARH 的喙部没有发现差异。在第二个实验中，使用 S-35 标记和地高辛标记的反义互补 RNA 探针，在哺乳动物中进行 AGRP 和 NPY 双标记原位杂交，以确定两种肽在 ARH 中的共定位程度。结果发现，整个 ARH 中几乎所有 NPY 阳性神经元也表达 AGRP mRNA 信号。此外，AGRP 表达几乎只限于 NPY 阳性神经元。因此，本研究表明，在哺乳期间，ARH 中一部分 AGRP 神经元中的 AGRP 基因表达显着升高。 AGRP 和 NPY 的高度共定位，加上我们实验室之前的报告表明，ARH 中 NPY 表达因哺乳而增加，表明 AGRP 和 NPY 是协调调节的，可能与哺乳期间食物摄入量的增加有关。
During lactation, the levels of neuropeptide Y (NPY), which plays an important role in mediating food intake, are significantly elevated in a number of hypothalamic areas, including the arcuate nucleus (ARH). To identify additional hypothalamic systems that might be important in mediating the increase in food intake and alterations in energy homeostasis during lactation, the present studies examined the expression of agouti-related protein (AGRP), a recently described homologue of the skin agouti protein. AGRP is found in the hypothalamus and has been suggested to play an important role in the regulation of food intake. In the first experiment, animals were studied during diestrus of the estrous cycle, a stage of the cycle when estrogen levels are basal and similar to lactation, or during days 12-13 postpartum. Lactating animals had their litters adjusted to eight pups on day 2 postpartum. Brain tissue sections were used to measure AGRP messenger RNA (mRNA) levels by in situ hybridization. AGRP mRNA signal was found mostly in the ventromedial portion of the ARH, which has been shown to contain a high density of NPY neurons. A significant increase in AGRP mRNA content was observed in the mid- to caudal portion of the ARH of lactating animals compared with diestrous females. No difference was found in the rostral portion of the ARH. In the second experiment, double-label in situ hybridization for AGRP and NPY was performed in lactating animals to determine the extent of colocalization of the two peptides in the ARH, using S-35-labeled and digoxigenin-labeled antisense complementary RNA probes. It was found that almost all of the NPY-positive neurons throughout the ARH also expressed AGRP mRNA signal. Furthermore, AGRP expression was confined almost exclusively to NPY-positive neurons. Thus, the present study showed that during lactation, AGRP gene expression was significantly elevated in a subset of the AGRP neurons in the ARH. The high degree of colocalization of AGRP and NPY, coupled with previous reports from our laboratory demonstrating increased NPY expression in the ARH in response to suckling, suggests that AGRP and NPY are coordinately regulated and may be involved in the increase in food intake during lactation.