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首页> 外文期刊>Developmental cell >Membrane-localized estrogen receptor α is required for normal organ development and function
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Membrane-localized estrogen receptor α is required for normal organ development and function

机译：正常器官发育和功能需要膜定位的雌激素受体α

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摘要

Steroid receptors are found in discrete cellular locations, but it is unknown whether extranuclear pools are necessary for normal organ development. To assess this, we developed a point mutant estrogen receptor α (ERα) knockin mouse (C451A) that precludes palmitoylation and membrane trafficking of the steroid receptor in all organs. Homozygous knockin female mice (nuclear-only ERα [NOER]) show loss of rapid signaling that occurs from membrane ERα in wild-type mice. Multiple developmental abnormalities were found, including infertility, relatively hypoplastic uteri, abnormal ovaries, stunted mammary gland ductal development, and abnormal pituitary hormone regulation in NOER mice. These abnormalities were rescued in heterozygous NOER mice that were comparable to wild-type mice. mRNAs implicated in organ development were often poorly stimulated by estrogen only in homozygous NOER mice. We conclude that many organs require membrane ERα and resulting signal transduction to collaborate with nuclear ERα for normal development and function.
机译：类固醇受体存在于离散的细胞位置，但尚不清楚核外池是否对于正常器官发育是必需的。为了评估这一点，我们开发了一种点突变雌激素受体α（ERα）敲入小鼠（C451A），该小鼠可以阻止所有器官中类固醇受体的棕榈酰化和膜运输。纯合敲入雌性小鼠（仅核ERα[NOER]）显示出野生型小鼠中因膜ERα引起的快速信号传导丧失。在NOER小鼠中发现了多种发育异常，包括不孕，相对相对子宫发育不良，卵巢异常，乳腺导管发育不良以及垂体激素调节异常。在与野生型小鼠相当的杂合NOER小鼠中挽救了这些异常。仅在纯合的NOER小鼠中，牵涉器官发育的mRNA通常很少被雌激素刺激。我们得出的结论是，许多器官都需要膜ERα及其产生的信号转导才能与核ERα协同作用，以实现正常发育和功能。

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