The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus.

The expression of select genes necessary for membrane-associated estrogen receptor signaling differ by sex in adult rat hippocampus.
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DOI:
10.1016/j.steroids.2017.09.012
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发表时间:
2019-03
期刊:
影响因子:
2.7
通讯作者:
Mermelstein PG
Mermelstein PG
中科院分区:
医学3区
文献类型:
--
作者:
Meitzen J;Britson KA;Tuomela K;Mermelstein PG

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17β-雌二醇可通过膜雌激素受体(ER)以性别特异性方式快速调节神经元功能。例如,雌性大鼠海马神经元表达与质膜相关的棕榈酰化形式的ERα和ERβ。这些膜相关ER由小窝蛋白组织成具有代谢型谷氨酸受体(mGluRs)的功能性信号微域。ER/mGluR信号转导介导了几种性别特异性雌二醇对海马神经元功能的作用。一个重要的未回答的问题是关于性别特异性膜相关的ER信号的产生机制,特别是因为以前已经证明mGluR的作用不是性别特异性的。一种可能性是ER膜复合物所必需的基因在男性和女性之间差异表达,包括编码ERα和ER β、小窝蛋白1和小窝蛋白3和/或棕榈酰酰基转移酶DHHC-7和DHHC-21的基因。因此,我们使用qPCR来检验这些基因在新生大鼠和成年大鼠海马中的表达中显示性别差异的假设。作为额外的对照,我们测试了与ER没有已知联系的20种其他DHHC棕榈酰酰基转移酶的表达。在新生儿海马,没有性别差异的基因表达。在成年海马体中,与男性相比,编码小窝蛋白1和DHHC-7的基因在女性中的表达降低。因此,选择基因不同性别在特定的发展阶段,主张一个更微妙的模型比简单的广泛围产期出现的性别差异,使性别特异性雌二醇的行动在所有基因。这些发现使得产生新的假设,关于膜相关的ER信号的性别差异编程的机制。
17β-estradiol can rapidly modulate neuron function via membrane estrogen receptors (ERs) in a sex-specific manner. For example, female rat hippocampal neurons express palmitoylated versions of ERα and ERβ that associate with the plasma membrane. These membrane-associated ERs are organized by caveolin proteins into functional signaling microdomains with metabotropic glutamate receptors (mGluRs). ER/mGluR signaling mediates several sex-specific estradiol actions on hippocampal neuron function. An important unanswered question regards the mechanism by which sex-specific membrane-associated ER signaling is generated, especially since it has been previously demonstrated that mGluR action is not sex-specific. One possibility is that the genes necessary for the ER membrane complex are differentially expressed between males and females, including genes that encode ERα and β, caveolin 1 and 3, and/or the palmitoylacyltransferases DHHC-7 and -21. Thus we used qPCR to test the hypothesis that these genes show sex differences in expression in neonatal and adult rat hippocampus. As an additional control we tested the expression of the 20 other DHHC palmitoylacyltransferases with no known connections to ER. In neonatal hippocampus, no sex differences were detected in gene expression. In adult hippocampus, the genes that encode caveolin 1 and DHHC-7 showed decreased expression in females compared to males. Thus, select genes differ by sex at specific developmental stages, arguing for a more nuanced model than simple widespread perinatal emergence of sex differences in all genes enabling sex-specific estradiol action. These findings enable the generation of new hypotheses regarding the mechanisms by which sex differences in membrane-associated ER signaling are programmed.
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