ROLE OF ALPHA & BETA ESTROGEN RECEPTORS IN AGGRESSION

描述：(改编自《调查者摘要》)一切顺利 确定了在社会冲突中，睾丸激素会促进攻击性， 通常见于雄鼠之间。睾酮发挥其神经作用不是 仅通过激活雄激素受体(AR)，作为其原始形式或AS 5α-还原代谢物，双氢睾酮，但也通过 雌激素受体(ER)，在芳香化成雌二醇后。一直以来 前面描述了在测试时ER的激活以及 在围产期发育中起着关键作用的诱导 雄性小鼠的攻击行为，并决定了雄性小鼠的性别差异 睾丸激素诱导的攻击性水平。两种形式的急诊室，一个经典的 ER-α和最近发现的ER-β定位于大脑区域 已知与睾丸激素诱导的攻击性有关。主要目标 建议的研究之一是确定ER-α所起的具体作用 和ER-β在攻击行为的调节中的作用。 在第一部分中，我们将确定ER-β激活在 成年测试时间在男性攻击行为调节中的作用 小鼠：1)比较雌激素诱导的攻击性ER-β水平 基因敲除(BERKO)小鼠(ER-α特异性激活)与其 野生型窝产仔(BWT；ER-α和ER-β激活)；以及2)检测 ER-β受体特异性激动剂对小鼠攻击行为的影响 WT雄性小鼠的ER-α特异性激动剂或AR特异性激动剂。在 提案的第二部分，我们将确定ER-α和 ER-β在睾酮诱导的攻击(对雄性入侵小鼠)中的作用 雌性老鼠。睾酮治疗的效果将在三个月内进行测试 基因敲除小鼠的类型：ER-α基因敲除(AERKO)、BERKO和双基因敲除 ER-α和ER-β基因(DERKO)。在提案的第三部分， 将测试AERKO雌性小鼠“内源性”致敏的可能性 通过提高睾酮水平作为一种 ER-α基因破坏的结果。在最后一部分中，我们将测试 假设新生儿ER-α而不是ER-β的激活决定了 睾酮及其促攻性作用的反应性 通过控制女性新生儿的类固醇水平，成年期的代谢物 老鼠。 拟议研究的结果将提供关于 这两种类型的环境保护机构在 性腺类固醇对攻击行为的性别特异性调节。

DESCRIPTION: (Adapted from the Investigator's Abstract) It has been well established that testosterone facilitates aggression during social conflict, typically seen between male mice. Testosterone exerts its neural action not only by activating androgen receptors (AR), as its original form or as 5alpha-reduced metabolite, dihydrotesterone, but also by acting through estrogen receptors (ER), after being aromatized to estradiol. It has been previously described that activation of ER at the time of testing as well as during perinatal development plays a critical role in the induction of aggressive behavior in male mice and determines the sex differences in the levels of testosterone-inducible aggression. Two forms of ERs, a classical ER-alpha and a recently discovered ER-beta, are localized in the brain areas known to be involved in testosterone-inducible aggression. The main objective of the proposed studies is to determine the specific roles played by ER-alpha and ER-beta in the regulation of aggressive behavior. In the first part, we will determine the role of ER-beta activation, at the time of testing in adulthood, in the regulation of aggressive behavior of MALE mice by: 1) comparing the levels of estrogen-inducible aggression of ER-beta gene knockout (BERKO) mice (ER-alpha specific activation) with those of their wild type littermates (BWT; ER-alpha and ER-beta activation); and 2) examining the effects of an ER-beta specific agonist on aggressive behavior induced by an ER-alpha specific agonist or an AR-specific agonist in WT male mice. In the second part of the proposal, we will determine the roles of ER-alpha and ER-beta in testosterone-inducible aggression (toward male intruder mice) in FEMALE mice. The effects of testosterone treatment will be tested in three types of knockout mice: ER-alpha knockout (aERKO), BERKO, and double knockout of ER-alpha and ER-beta genes (dERKO). In the third part of the proposal, the possibility will be tested that aERKO FEMALE mice are "endogenously" sensitized for testosterone-inducible aggression by elevated levels of testosterone as a result of ER-alpha gene disruption. In the last part, we will test the hypothesis that neonatal ER-alpha, but not ER-beta, activation determines the responsiveness to aggression-promoting action of testosterone and its metabolites in adulthood, by manipulating neonatal steroid levels in FEMALE mice. The findings of the proposed studies will provide new insights concerning the specific roles and mechanisms played by the two types of ERs in the sex-specific regulation of aggressive behavior by gonadal steroids.