Effect of a putative ERalpha antagonist, MPP, on food intake in cycling and ovariectomized rats.
Effect of a putative ERalpha antagonist, MPP, on food intake in cycling and ovariectomized rats.
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DOI：
10.1016/j.physbeh.2009.02.021
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发表时间：
2009-05-25
影响因子：
2.9
通讯作者：
Eckel, Lisa A.
中科院分区：
文献类型：
--
作者：
Santollo, Jessica;Eckel, Lisa A.
雌激素通过与核雌激素受体（ER）蛋白ERα和ERβ结合发挥其许多行为效应。最近的ER基因敲除小鼠和选择性ER激动剂的研究表明，雌二醇的促凋亡作用是通过激活ERα介导的。为了研究这一假说，我们检测了假定的ERα拮抗剂MPP是否能阻断雌二醇的促凋亡作用。在第一系列实验中，监测MPP对卵巢切除（OVX）大鼠摄食量和子宫重量的影响，这些大鼠接受生理剂量的苯甲酸雌二醇（EB）或选择性ERα激动剂（PPT）治疗。在最终实验中，在卵巢完整（循环）雌性大鼠中急性给予MPP后监测摄食量。与我们的假设相反，MPP未能减弱EB或PPT的能力，减少食物摄入量和增加子宫重量OVX大鼠。然而，在卵巢完整的大鼠中，类似的MPP治疗方案减弱了与发情相关的摄食量阶段性减少。我们的结论是，MPP可能是一个有用的工具，调查内源性雌二醇的行为作用，但可能有有限的效用在研究外源性雌二醇在OVX大鼠的行为效应。
Estrogens exert many of their behavioral effects by binding to nuclear estrogen receptor (ER) proteins, ERα and ERβ. Recent studies involving ER knockout mice and selective ER agonists suggest that estradiol’s anorexigenic effect is mediated via activation of ERα. To investigate this hypothesis, we examined whether the presumptive ERα antagonist, MPP, could block estradiol’s anorexigenic effect. In the first series of experiments, the effects of MPP on food intake and uterine weight were monitored in ovariectomized (OVX) rats treated with either a physiological dose of estradiol benzoate (EB) or a selective ERα agonist (PPT). In the final experiment, food intake was monitored following acute administration of MPP in ovarian-intact (cycling) female rats. Contrary to our hypothesis, MPP failed to attenuate either EB’s or PPT’s ability to decrease food intake and increase uterine weight in OVX rats. However, in ovarian-intact rats, a similar regimen of MPP treatment attenuated the phasic decrease in food intake that is associated with estrus. We conclude that MPP may be a useful tool to investigate the behavioral actions of endogenous estradiol, but may have limited utility in studying the behavioral effects of exogenous estradiol in OVX rats.
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