Div. of Urology, Dept. of Surgery, Taichung Veterans General Hospital, 1650, Taiwan Blvd. Section 4, Taichung, Taiwan 40705, Republic of China.
Am J Physiol Renal Physiol. 2014 Jan;306(2):F181-7. doi: 10.1152/ajprenal.00298.2013. Epub 2013 Nov 20.
The postmenopausal hypoestrogen status induces various lower urinary tract dysfunctions. Ovariectomized (OVX) rats exhibit voiding abnormalities, including increased postvoiding residual urine (PVR), decreased voiding efficiency (VE), and altered coordination between the detrusor and external urethral sphincter (EUS). Estradiol replacement partially normalizes voiding function in OVX rats. We determined if selective agonists for estrogen receptor (ER)α and/or ERβ can reverse lower urinary tract dysfunction in OVX rats. Cystometry and EUS electromyograms (EMGs) were recorded 6 wk after bilateral OVX in urethane-anesthetized female Sprague-Dawley rats. Animals received daily subcutaneous injections of selective ERα [propylpyrazole triol (PPT)] or ERβ [diarylpropionitrile (DPN)] agonists or vehicle for 1 wk starting on the fifth week after OVX. PPT (1 mg·kg(-1)·day(-1)) decreased PVR, improved VE, and shortened the EUS EMG active period (AP) during voiding. DPN (2 or 5 mg·kg(-1)·day(-1)) did not alter cystometric parameters or EUS EMG activity. Combined PPT + DPN treatment elicited changes in PVR, VE, and AP, similar to those induced by PPT alone, but also increased the EUS EMG silent period and volume threshold for triggering micturition. PPT increased uterine weight fourfold and decreased body weight by 11%. DPN increased uterine weight 30-45% but decreased body weight by 3-5%. Reduced voiding efficiency in OVX rats can be reversed by 1-wk drug treatment that selectively targets ERα and reduces AP during EUS bursting. Combined pharmacological activation of ERα and ERβ further enhanced EUS bursting by increasing the EUS EMG silent period and also facilitated bladder storage mechanisms by increasing the volume threshold.
绝经后低雌激素状态会引起各种下尿路功能障碍。去卵巢（OVX）大鼠表现出排尿异常，包括排尿后残余尿量增加（PVR）、排尿效率降低（VE）以及逼尿肌和尿道外括约肌（EUS）之间协调改变。雌二醇替代部分可使 OVX 大鼠的排尿功能正常化。我们确定雌激素受体（ER）α和/或 ERβ的选择性激动剂是否可以逆转 OVX 大鼠的下尿路功能障碍。在乌拉坦麻醉的雌性 Sprague-Dawley 大鼠双侧 OVX 后 6 周，记录膀胱测压和 EUS 肌电图（EMG）。动物在 OVX 后第 5 周开始，每天接受皮下注射选择性 ERα [丙基吡唑三醇（PPT）]或 ERβ [二芳基丙腈（DPN）]激动剂或载体，持续 1 周。PPT（1 mg·kg(-1)·day(-1)）降低了 PVR，改善了 VE，并缩短了排尿时的 EUS EMG 活跃期（AP）。DPN（2 或 5 mg·kg(-1)·day(-1)）并未改变膀胱测压参数或 EUS EMG 活动。联合 PPT+DPN 治疗可引起 PVR、VE 和 AP 的变化，与单独使用 PPT 引起的变化相似，但也增加了 EUS EMG 安静期和触发排尿的容积阈值。PPT 使子宫重量增加了四倍，体重减轻了 11%。DPN 使子宫重量增加了 30-45%，但体重减轻了 3-5%。OVX 大鼠的排尿效率降低可通过 1 周的药物治疗逆转，该治疗选择性靶向 ERα 并减少 EUS 爆发时的 AP。ERα 和 ERβ 的联合药理激活通过增加 EUS EMG 安静期进一步增强了 EUS 爆发，并通过增加容积阈值促进了膀胱储存机制。
