Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells: Interactions with glucose and glucocorticoids
Lactogenic and somatogenic hormones regulate the expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript in rat insulinoma (INS-1) cells: Interactions with glucose and glucocorticoids
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DOI：
10.1210/en.2006-0888
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Freemark, Michael
中科院分区：
文献类型：
--
作者：
Arumugam, Ramamani;Fleenor, Don;Freemark, Michael
催乳激素刺激啮齿动物、有蹄类动物和鸟类的食物摄入。为了验证催乳素调节控制食欲的神经肽表达的假设，我们使用催乳素（PRL）反应性大鼠胰岛素瘤（INS-1）细胞系作为实验范例。INS-1细胞表达神经肽Y（NPY）和可卡因和安非他明调节转录物（CART）的mRNA，但很少或没有刺豚鼠相关肽或阿黑皮素原。与体内下丘脑一样，葡萄糖剥夺可使INS-1细胞中NPY mRNA水平升高。相反，高培养基葡萄糖浓度（11 mM）降低了NPY mRNA的水平，并增加了CART mRNA的水平。大鼠PRL刺激INS-1细胞中NPY mRNA增加4- 7倍（P < 0.001），并使CART mRNA水平降低50-80%（P < 0.001）。PRL对神经肽Y mRNA表达的影响呈时间和剂量依赖性，并可被葡萄糖剥夺或外源性地塞米松（Dex）加强。NPY mRNA的激素诱导伴随着NPY肽分泌到细胞条件培养基中的增加。PRL刺激AMP活化蛋白激酶（AMPK）表达增加1.8至3.5倍，AMPK部分介导低血糖对下丘脑中NPY表达的影响。AMPK活性的药理学抑制使PRL对NPY和CART的作用轻微减弱，但完全逆转了Dex或PRL加Dex对CART mRNA的作用。PRL对NPY、CART和AMPK mRNA的影响与其他催乳素和生长激素（包括胎盘催乳素和GH）的影响相一致。大鼠PRL和大鼠GH的组合没有添加剂或协同作用，这表明催乳激素和促生长激素通过类似的机制调节神经肽基因的表达。我们的结论是催乳素与葡萄糖剥夺和糖皮质激素共同作用，诱导NPY表达并抑制CART。我们推测，催乳素促进食物的摄入，以响应空腹或营养缺乏，当葡萄糖水平下降和皮质醇水平上升。
Lactogenic hormones stimulate food intake in rodents, ungulates, and birds. To test the hypothesis that lactogens regulate expression of neuropeptides that control appetite, we used the prolactin (PRL)-responsive rat insulinoma (INS-1) cell line as an experimental paradigm. INS-1 cells express mRNA for neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) but little or no agouti-related peptide or proopiomelanocortin. As in the hypothalamus in vivo, the levels of NPY mRNA in INS-1 cells were increased by glucose deprivation. Conversely, high media glucose concentrations (11 mM) reduced the levels of NPY mRNA and increased levels of CART mRNA. Rat PRL stimulated a 4- to 7-fold increase in NPY mRNA in INS-1 cells (P < 0.001) and reduced by 50-80% the levels of CART mRNA (P < 0.001). The effects of PRL on NPY mRNA were time and dose dependent and potentiated by glucose deprivation or exogenous dexamethasone (Dex). Hormonal induction of NPY mRNA was accompanied by increased secretion of NPY peptide into cellular conditioned media. PRL stimulated a 1.8- to 3.5-fold increase in expression of AMP-activated protein kinase (AMPK), which mediates in part the effects of hypoglycemia on NPY expression in the hypothalamus in vivo. Pharmacological inhibition of AMPK activity blunted slightly the effects of PRL on NPY and CART but reversed entirely the effects of Dex or of PRL plus Dex on CART mRNA. The effects of PRL on NPY, CART, and AMPK mRNA were mirrored by those of other lactogens and somatogens including placental lactogen and GH. Rat PRL and rat GH in combination had no additive or synergistic effects, suggesting that lactogenic and somatogenic hormones regulate neuropeptide gene expression through similar mechanisms. We conclude that lactogens act in concert with glucose deprivation and glucocorticoids to induce NPY expression and inhibit CART. We speculate that the lactogens facilitate food intake in response to fasting or nutrient deprivation, when glucose levels decline and cortisol levels rise.