Brain astrocytes are implicated in estrogenic neuroprotection against bio-energetic insults, which may involve their glycogen energy reserve. Forebrain estrogen receptors (ER)-alpha (ERα) and -beta (ERβ) exert differential control of glycogen metabolic enzyme [glycogen synthase (GS); phosphorylase (GP)] expression in hypoglycemic male versus female rats. Studies were conducted using a rat hypothalamic astrocyte primary culture model along with selective ER agonists to investigate the premise that estradiol (E2) exerts sex-dimorphic control over astrocyte glycogen mass and metabolism. Female astrocyte GS and GP profiles are more sensitive to E2 stimulation than the male. E2 did not regulate expression of phospho-GS (inactive enzyme form) in either sex. Data also show that transmembrane G protein-coupled ER-1 (GPER) signaling is implicated in E2 control of GS profiles in each sex and alongside ERα, GP expression in females. E2 increases total 5'-AMP-activated protein kinase (AMPK) protein in female astrocytes, but stimulated pAMPK (active form) expression with equivalent potency via GPER in females and ERα in males. In female astrocytes, ERα protein was up-regulated at a lower E2 concentration and over a broader dosage range compared to males, whereas ERβ was increased after exposure to 1-10 nM versus 100 pM E2 levels in females and males, respectively. GPER profiles were stimulated by E2 in female, but not male astrocytes. E2 increased astrocyte glycogen content in female, but not male astrocytes; selective ERβ or ERα stimulation elevated glycogen levels in the female and male, respectively. Outcomes imply that dimorphic astrocyte ER and glycogen metabolic responses to E2 may reflect, in part, differential steroid induction of ER variant expression and/or regulation of post-receptor signaling in each sex.

中文翻译：

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大鼠下丘脑星形胶质细胞雌激素受体表达和糖原代谢的性别特异性雌激素调节。

脑星形胶质细胞参与针对生物能性损伤的雌激素神经保护作用，这可能涉及其糖原能量储备。前脑雌激素受体（ER）-α（ERα）和-β（ERβ）对糖原代谢酶[糖原合酶（GS）；磷酸化酶（GP）]在低血糖雄性和雌性大鼠中的表达。使用大鼠下丘脑星形胶质细胞原代培养模型以及选择性的ER激动剂进行研究，以研究雌二醇（E2）对星形胶质糖原质量和代谢进行性别二态控制的前提。雌性星形胶质细胞的GS和GP分布比雄性更敏感。E2在任何性别中均不调节磷酸-GS（失活酶形式）的表达。数据还表明，跨膜G蛋白偶联的ER-1（GPER）信号与男女性别中的GS分布的E2控制以及雌性中的ERα，GP表达有关。E2增加雌性星形胶质细胞中的总5'-AMP激活的蛋白激酶（AMPK）蛋白，但通过雌性的GPER和雄性的ERα刺激pAMPK（活性形式）的表达具有同等效力。在雌性星形胶质细胞中，与雄性相比，ERα蛋白在较低的E2浓度和更大的剂量范围内被上调，而在雌性和雄性中，暴露于1-10 nM的ERβ相对于100 pM E2则增加。在雌性而不是雄性星形胶质细胞中，E2刺激了GPER分布。E2增加雌性星形胶质细胞中星形胶质糖原含量，但不增加雄性星形胶质细胞；选择性ERβ或ERα刺激分别提高了女性和男性的糖原水平。