Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model.
Effects of two estradiol regimens on anxiety and depressive behaviors and trophic effects in peripheral tissues in a rodent model.
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DOI：
10.1016/j.genm.2009.04.004
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Frye CA
中科院分区：
文献类型：
--
作者：
Walf AA;Frye CA
随着年龄的增长和绝经，这与卵巢类固醇如17β-雌二醇（E2）的减少有关，女性可能会出现消极的心理症状，包括焦虑和抑郁。一些女性使用基于E2的疗法来缓解这些症状，但E2与营养效应相关，可能会增加绝经前和绝经后女性对某些类固醇敏感性癌症（如乳腺癌）的易感性。本研究采用E2下降和替代的动物模型，探讨了E2对焦虑和抑郁行为的可能有益作用与营养效应之间的关系。研究了E2对年轻成年大鼠的情感、性和运动行为的剂量依赖性影响。卵巢切除（OVX）大鼠通过管饲法给予化学致癌物7，12-二甲基苯并（a）蒽（DMBA）1.25 mg或非活性溶剂（植物油;对照）。E2（0.03或0.09 mg/kg）或溶剂在评估焦虑（明暗过渡）、抑郁（强迫游泳试验）、性（脊柱前凸）和运动（活动监测）行为前44 - 48小时皮下给药。致癌物暴露后14周，测定血浆和脑区（皮质、海马和下丘脑）中的E2浓度。分析肿瘤发生率、肿瘤数量和子宫重量。与E2（0.03 mg/kg）和溶剂相比，E2（0.09 mg/kg）给药与明-暗转换任务中的抗焦虑样行为、强迫游泳测试中的抗抑郁样行为以及生理循环和中枢E2浓度的显着增加相关。与溶剂相比，E2（0.9 > 0.3 mg/kg）与脊柱前凸和子宫重量显着增加相关。施用DMBA与肿瘤发生率和数量的显著增加相关; E2施用增强了这种效果。基于在该大鼠模型中的发现，支持了E2可能有效减少OVX大鼠的焦虑和抑郁行为并增强性行为的假设，同时在外周具有营养作用。中等生理水平的E2可能对雌性啮齿动物的情感和性行为有有益的影响，但包括E2的方案可能会增加致瘤能力。
With aging and menopause, which are associated with decreases in ovarian steroids such as 17β-estradiol (E2), women might experience negative psychological symptoms, including anxiety and depression. Some women use E2-based therapies to alleviate these symptoms, but E2 has been associated with trophic effects that might increase vulnerability to some steroid-sensitive cancers, such as breast cancer, in both premenopausal and postmenopausal women. This study investigated the relationships between the possible beneficial effects of E2 on anxiety and depressive behaviors concurrent with trophic effects using an animal model of E2 decline and replacement. Dose-dependent effects of E2 on affective, sexual, and motor behavior of young adult rats were studied. Ovariectomized (OVX) rats were administered the chemical carcinogen 7,12-dimethylbenz(a) anthracene (DMBA) 1.25 mg or inactive vehicle (vegetable oil; control) by gavage. E2 (0.03 or 0.09 mg/kg) or vehicle was administered subcutaneously 44 to 48 hours before assessments of anxiety (light–dark transition), depression (forced swim test), sexual (lordosis), and motor (activity monitor) behaviors. Fourteen weeks after carcinogen exposure, E2 concentrations in plasma and brain regions (cortex, hippocampus, and hypothalamus) were determined. Incidences and numbers of tumors and uterine weight were analyzed. Administration of E2 (0.09 mg/kg) was associated with significant increases in antianxiety-like behavior in the light–dark transition task, antidepressant-like behavior in the forced swim test, and physiologic circulating and central E2 concentrations compared with E2 (0.03 mg/kg) and vehicle. Compared with vehicle, E2 (0.9 > 0.3 mg/kg) was associated with significant increases in lordosis and uterine weight. Administration of DMBA was associated with significant increases in the incidences and numbers of tumors; this effect was augmented by E2 administration. Based on the findings in this rat model, the hypothesis that E2 may be effective in reducing anxiety and depressive behaviors and enhance sexual behavior in OVX rats, concurrent with trophic effects in the periphery, was supported. Moderate physiologic levels of E2 might have beneficial effects on affective and sexual behaviors in female rodents, but regimens including E2 might increase tumorigenic capacity.
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影响因子：
158.5
作者：
COLDITZ, GA;HANKINSON, SE;SPEIZER, FE
通讯作者：
SPEIZER, FE
影响因子：
3.5
作者：
Frye, CA;Walf, AA
通讯作者：
Walf, AA
影响因子：
3.8
作者：
Lambe, M;Hsieh, CC;Adami, HO
通讯作者：
Adami, HO
DOI：
10.1093/jnci/87.22.1681
发表时间：
1995-11-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MADIGAN, MP;ZIEGLER, RG;HOOVER, RN
通讯作者：
HOOVER, RN
影响因子：
7.2
作者：
Almeida, OP;Lautenschlager, N;Flicker, L
通讯作者：
Flicker, L