Santollo Jessica, Eckel Lisa A
Program in Neuroscience and Department of Psychology, Florida State University, Tallahassee, FL 32306-1270, USA.
Physiol Behav. 2009 May 25;97(2):193-8. doi: 10.1016/j.physbeh.2009.02.021. Epub 2009 Feb 28.
Estrogens exert many of their behavioral effects by binding to nuclear estrogen receptor (ER) proteins, ERalpha and ERbeta. Recent studies involving ER knockout mice and selective ER agonists suggest that estradiol's anorexigenic effect is mediated via activation of ERalpha. To investigate this hypothesis, we examined whether the presumptive ERalpha 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 ERalpha 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.
雌激素通过与核雌激素受体（ER）蛋白，即ERα和ERβ结合，发挥其诸多行为效应。近期涉及ER基因敲除小鼠和选择性ER激动剂的研究表明，雌二醇的厌食效应是通过激活ERα介导的。为了验证这一假说，我们研究了假定的ERα拮抗剂MPP是否能阻断雌二醇的厌食效应。在第一组实验中，监测了用生理剂量苯甲酸雌二醇（EB）或选择性ERα激动剂（PPT）处理的去卵巢（OVX）大鼠中MPP对食物摄入量和子宫重量的影响。在最后一项实验中，监测了卵巢完整（处于发情周期）的雌性大鼠急性给予MPP后的食物摄入量。与我们的假说相反，MPP未能减弱EB或PPT在OVX大鼠中减少食物摄入量和增加子宫重量的能力。然而，在卵巢完整的大鼠中，类似的MPP处理方案减弱了与发情期相关的食物摄入量的阶段性减少。我们得出结论，MPP可能是研究内源性雌二醇行为作用的有用工具，但在研究外源性雌二醇对OVX大鼠行为效应方面可能效用有限。
