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首页> 外文期刊>Molecular and Cellular Biology >Genetic Ablation of the Steroid Receptor Coactivator-Ubiquitin Ligase, E6-AP, Results in Tissue-Selective Steroid Hormone Resistance and Defects in Reproduction
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Genetic Ablation of the Steroid Receptor Coactivator-Ubiquitin Ligase, E6-AP, Results in Tissue-Selective Steroid Hormone Resistance and Defects in Reproduction

机译：类固醇受体共激活因子-泛素连接酶，E6-AP的遗传消融导致组织选择性类固醇激素抵抗和繁殖缺陷。

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The E6-associated protein (E6-AP), although originally identified as a ubiquitin ligase, has recently been shown to function as a coactivator of steroid receptor-dependent gene expression in in vitro assays. In order to determine whether E6-AP acts as a coactivator in vivo, physiological parameters associated with male and female sex steroid action were assessed in the E6-AP null mouse. Gonadal size was reduced in E6-AP null male and female mice in comparison to wild-type controls in conjunction with reduced fertility in both genders. Consistent with this observation, defects in sperm production and function, as well as ovulation were observed. In comparison to wild-type controls, induction of prostate gland growth induced by testosterone and uterine growth by estradiol were significantly reduced. In contrast, estrogen and progesterone-stimulated growth of virgin mammary gland was not compromised by E6-AP ablation despite E6-AP expression in this tissue. This latter finding contrasts with the impaired estrogen and progesterone-induced mammary gland development observed previously for steroid receptor coactivator type 1 (SRC-1) and SRC-3 female knockout mice. Taken together, these results are consistent with a role for E6-AP in mediating a subset of steroid hormone actions in vivo. Nevertheless, differences observed between SRC and E6-AP knockout phenotypes indicate that these two families of steroid receptor coactivators are not functionally equivalent and supports the hypothesis that coactivators contribute to tissue-specific steroid hormone action.
机译：尽管最初被鉴定为泛素连接酶，但与E6相关的蛋白（E6-AP）最近在体外试验中显示出可作为类固醇受体依赖性基因表达的共激活因子。为了确定E6-AP是否在体内起共激活剂的作用，在E6-AP无效小鼠中评估了与雄性和雌性类固醇作用相关的生理参数。与野生型对照相比，E6-AP无效的雄性和雌性小鼠的性腺大小均减小，并且两性生育力均降低。与该观察结果一致，观察到精子产生和功能以及排卵的缺陷。与野生型对照相比，由睾丸激素诱导的前列腺生长诱导和由雌二醇引起的子宫生长显着减少。相比之下，尽管E6-AP在组织中表达，但雌激素和孕激素刺激的原始乳腺的生长不受E6-AP消融的影响。后一个发现与先前观察到的类固醇受体共激活因子1型（SRC-1）和SRC-3雌性敲除小鼠的雌激素和孕激素诱导的乳腺发育受损形成对照。两者合计，这些结果与E6-AP在体内体内介导类固醇激素作用的作用中一致。尽管如此，在SRC和E6-AP基因敲除表型之间观察到的差异表明，这两个类固醇受体共激活因子在功能上并不相同，并支持了该共激活因子有助于组织特异性类固醇激素作用的假设。

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