中文摘要：

目的 初步探讨雌激素β受体（estrogen receptor beta,ERβ）在小鼠海马不同发育时期的表达以及ERβ活性改变对actin细胞骨架聚合调节蛋白表达的影响及其机制。方法 C57BL/6小鼠按性别和出生后时间[出生后0（P0）、7（P7）、14（P14）、28（P28）、56 d（P56）]分为10组,用免疫组化和Western blot检测小鼠海马中ERβ的表达变化。另取动情间期成年雌性C57BL/6小鼠用随机数字表法分为5组：对照组和腹腔注射ERβ活性抑制剂PHTPP（100μg/kg）1、3、5、7 d组。再取同种小鼠用随机数字表法分为5组：假手术对照组,卵巢切除（ovariectomy,OVX）组,OVX 1周后再皮下注射ERβ活性激动剂DPN 1.25、2.5、5.0 mg/kg组,均连续注射1周。用免疫组织化学方法检测海马类固醇受体辅助活化因子-1（steroid receptor coactivator-1,SRC-1）的表达,用Western blot检测海马Rictor、磷酸化蛋白激酶B（phospho-protein kinase B,p-Akt）、Profilin-1、磷酸化cofilin（phospho-cofilin ser3,p-cofilin）和SRC-1的蛋白水平表达变化。结果 免疫组化和Western blot检测发现,ERβ在雌、雄小鼠海马P0组表达较高,P7组和P14组表达较P0组降低（P〈0.05）,而P28组和P56组ERβ表达较P7组和P14组升高（P〈0.01）。用PHTPP抑制ERβ活性导致Rictor、p-Akt、Profilin-1、p-cofilin和SRC-1的表达下降（P〈0.05）,而OVX导致上述分子表达下降可被ERβ活性激动剂DPN逆转（P〈0.05）。结论 从出生到成年小鼠海马内ERβ的表达呈U型变化。调节ERβ活性可诱导actin细胞骨架聚合调节蛋白及SRC-1的表达发生改变,提示ERβ可能通过SRC-1/Rictor/p-Akt途径对actin细胞骨架聚合状态进行调节并最终介导雌激素（estrogens,E2）对学习记忆的调节。

英文摘要：

Objective To detect the expression profile of estrogen receptor β（ERβ） in the postnatal hippocampus of male and female mice during development and investigate the underlying mechanism of ERβ activity on the regulation of actin polymerization related proteins. Methods C57BL/6 mice were divided into 10 groups by their sex and postnatal days （130, P7, P4,P28 and P56 ）. The expression of ERβ in the hippocampus was determined with immunohistochemical assay and Western blotting. Then adult female diestms C57BL/6 mice were randomly divided into 5 groups, that is, control and PHTPP （ERβ inhibitor） treatment groups （ 1, 3, 5 and 7 d）. DMSO and PHTPP （ 100 μg/kg） were intra-peritoneally injected. Then another 5 groups were treated respectively with DMSO, ovariectomy （OVX）, and DPN （ERβ activator,1.25, 2.5 or 5.0 mg/kg） subcutaneously in 1 week after OVX. hnmunohistochemical assay was used to examine the expression of steroid receptor eoactivator-1 （ SRC-1 ） , and Western blotting was employed to detect the expression of hippocampal Rictor, phospho-protein kinase B （p-Akt） , Profilin-1, phospho-eofilin ser3 （p-cofilin） and SRC-1. Results In both male and female hippoeampus, high ERβ level was found at PO, then the level was deereased to the lower level at P7 and P14 （P 〈 0.05 compared with PO ） and increased to the higher level at P28 and P56 （P 〈0.01 eompared with P7 and P14）. In the adult mice after 7 days＇ PHTPP treatment, the expression levels of Rietor, p-Akt, Profilin-1, p-eofilin and SRC-1 were signifieantly deereased （P 〈 0.05 ）. On the eontrary, these levels was decreased dramatically after OVX but were significantly rescued by the 7 days＇ DPN treatment （P 〈 0.05 ）. Conclusion Postnatal ERβ profile is in a U-shape trend in the hippocampus of mice. Manipulation of ERβ aetivity results in the alternations of SRC-I and actin cytoskeleton polymerization. This indicates ERβ may mediate estrogens regulation on learning and memory through SRC-1