Estrogen increases locomotor activity in mice through estrogen receptor α:: Specificity for the type of activity
Estrogen increases locomotor activity in mice through estrogen receptor α:: Specificity for the type of activity
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DOI：
10.1210/en.2002-220519
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发表时间：
2003-01-01
期刊：
影响因子：
4.8
通讯作者：
Pfaff, DW
中科院分区：
文献类型：
--
作者：
Ogawa, S;Chan, J;Pfaff, DW
已知雌激素主要通过作用于内侧视前区（mPOA）来增加啮齿动物的跑轮活动。这种雌激素调控跑步轮活动的机制尚不完全清楚。特别是，我们对两种雌激素受体erα和erβ的作用知之甚少，这两种受体都在mPOA神经元中表达。在本研究中，我们研究了持续雌激素治疗对erα (alphaERKO)或erβ (betaERKO)基因特异性缺失的雄性和雌性小鼠跑轮活动的影响。小鼠进行性腺切除术，1周后植入低剂量（16 ng/d）或高剂量（160 ng/d）苯甲酸雌二醇（EB）或安慰剂对照颗粒。从EB植入后10天开始，记录9 d的家笼跑轮活动。同样的小鼠在植入EB之前和之后也进行了野外活动测试。在雌性和雄性alphaERKO小鼠中，跑轮活动与安慰剂对照组中相应的野生型（alphat）小鼠没有区别。在雌性和雄性小鼠中，EB只在alphat小鼠中增加，而在alphaERKO小鼠中没有增加。另一方面，在betaERKO小鼠中，两种剂量的EB都增加了两性的跑步轮活动，就像在betaWT小鼠中一样。然而，eb治疗组的betaERKO女性的绝对每日转数明显低于alpha -t女性。在EB治疗前，性腺去角质的雌性alphaERKO在野外试验中明显低于阿尔法小鼠，而雌性betaERKO则倾向于比阿尔法小鼠更活跃。在雄性小鼠中，erα或erβ基因敲除对开阔场地活动没有影响。与对跑轮活动的影响不同，EB处理只诱导雌性小鼠的开阔场地活动小幅增加，而雄性小鼠则没有。结果表明：1)在两性中，雌激素对跑轮活动的调节主要通过ERa介导，而不是ERP；2)激素/基因型效应是特定于运动活动类型的（即家中笼跑轮活动和野外活动）。
Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERalpha and ERbeta, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERalpha (alphaERKO) or the ERbeta (betaERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male alphaERKO mice, running wheel activity was not different from that in corresponding wild-type (alphaWT) mice in placebo control groups. In both females and males it was increased by EB only in alphaWT, not alphaERKO, mice. In betaERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in betaWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in betaERKO females compared with alphaWT females. Before EB treatment, gonadectomized alphaERKO female were significantly less active than alphaWT mice in open field tests, whereas betaERKO females tended to be more active than alphaWT mice. In male mice there were no effect of ERalpha or ERbeta gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERa, not the ERP; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured.