Effects of Estrogen, Raloxifene and Levormeloxifene on α1A-Adrenergic Receptor Expression
Effects of Estrogen, Raloxifene and Levormeloxifene on α1A-Adrenergic Receptor Expression
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DOI：
10.1016/j.juro.2008.07.020
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发表时间：
2008-11-01
影响因子：
6.6
通讯作者：
Lin, Ching-Shwun
中科院分区：
文献类型：
--
作者：
Banie, Lia;Lin, Guiting;Lin, Ching-Shwun
目的：我们研究了雌激素、雷洛昔芬和左美洛昔芬对α1A-肾上腺素能受体表达的影响。材料和方法：产后大鼠接受阴道内球囊损伤和卵巢切除术，然后用雌激素或安慰剂治疗8周。通过蛋白质印迹分析和免疫组织化学检查尿道的α1A-肾上腺素能受体表达。从未经处理的雌性大鼠中分离尿道平滑肌细胞，并通过免疫荧光显微镜检查雌激素受体α和β的表达。用雌激素、雷洛昔芬或左美洛昔芬处理尿道平滑肌细胞 24 小时，并通过实时聚合酶链反应检查 α1A-肾上腺素能受体表达。通过启动子测定进一步检查这些药物对α1A-肾上腺素能受体表达的影响。结果：雌激素治疗导致尿道中α1A-肾上腺素能受体表达减少。尿道平滑肌细胞表达雌激素受体α和β，前者主要在细胞质中，后者在细胞核中。雌激素显着下调α1A-肾上腺素能受体mRNA表达，而雷洛昔芬和左美洛昔芬没有显着影响。在雌激素受体α或β存在的情况下，雌激素还显着下调α1A-肾上腺素能受体启动子。在雌激素受体α而非β存在的情况下，雷洛昔芬和左美洛昔芬上调α1A-肾上腺素受体启动子。结论：雌激素下调雌性大鼠尿道平滑肌中α1A-肾上腺素受体的表达，而雷洛昔芬和左美洛昔芬无明显影响。这些发现代表了雌激素、雷洛昔芬和左美洛昔芬对尿失禁产生不同影响的可能分子机制。
Purpose: We investigated the effect of estrogen, raloxifene and levormeloxiferie on alpha 1A-adrenergic receptor expression.Materials and Methods: Postpartum rats underwent intravaginal balloon injury and ovariectomy, and were then treated with estrogen or placebo for 8 weeks. The urethras were examined for alpha 1A-adrenergic receptor expression by Western blot analysis and immunohistochemistry. Urethral smooth muscle cells were isolated from untreated female rats and examined for the expression of estrogen receptors alpha and beta by immunofluorescence microscopy. Urethral smooth muscle cells were treated with estrogen, raloxifene or levormeloxifene for 24 hours and examined for alpha 1A-adrenergic receptor expression by real-time polymerase chain reaction. The effects of these drugs on alpha 1A-adrenergic receptor expression were further examined by promoter assays.Results: Estrogen treatment resulted in decreased alpha 1A-adrenergic receptor expression in the urethras. Urethral smooth muscle cells expressed estrogen receptors alpha and beta, the former predominantly in the cytoplasm and the latter in the nucleus. Estrogen significantly down-regulated alpha 1A-adrenergic receptor mRNA expression, while raloxifene and levormeloxifene had no significant effect. Estrogen also significantly down-regulated alpha 1A-adrenergic receptor promoter in the presence of estrogen receptor alpha or beta. Raloxifene and levormeloxifene up-regulated alpha 1A-adrenergic receptor promoter in the presence of estrogen receptor alpha but not beta.Conclusions: Estrogen down-regulated alpha 1A-adrenergic receptor expression in the urethral smooth muscle of female rats, while raloxifene and levormeloxifene had no significant effect. These findings represent a possible molecular mechanism through which estrogen, raloxifene and levormeloxifene differentially affect urinary continence.