Lin Alpha Dian-Yu, Levin Robert, Kogan Barry, Whitbeck Catherine, Chichester Paul, Sokol Rebekah, Mannikarottu Anita
Albany College of Pharmacy, Albany, New York 12208, USA.
Neurourol Urodyn. 2006;25(5):473-9. doi: 10.1002/nau.20258.
Estrogen is essential for physiological maintenance of the female urogenital tract. It is believed that alterations in female sex hormones play a major role in the etiology and response to urinary tract dysfunctions. In animal studies, ovariectomy (Ovx) results in smooth muscle (SM) weakness and atrophy whereas estrogen supplementation reverses these effects. Our study seeks to establish the mechanisms by which estrogen augmentation results in increased contractility.
Twenty New Zealand White female rabbits were separated into five groups of four each. Group 1 served as control, rabbits of groups 2-5 were ovariectomized, group 2 ovariectomized received no estradiol, groups 3-5 were given 17-beta estradiol (1 mg/kg/day) by subcutaneous slow release tablet implant for 1, 3, and 7 days, respectively, beginning 2 weeks after Ovx. At the end of the experimental period, each rabbit was anesthetized and the urinary bladder was removed for contractile, histological, and biochemical studies.
Ovx resulted in significantly decreased bladder contractile function, whereas bladders tested after estradiol administration showed increased contractility. Ovx resulted in a decrease in SM/collagen ratio, whereas estrogen resulted in an increase. The estrogen receptor (ER) density significantly increased following Ovx. After 1 day of estrogen treatment, the ER density decreased significantly below control levels, but rose progressively during the estrogen treatment.
The present study demonstrates that estrogen supplementation mediates a "functional hypertrophy," that is a hypertrophy characterized by increased contractile responses to all forms of stimulation, and an increased ratio of SM/collagen.
雌激素对于女性泌尿生殖道的生理维持至关重要。据信，女性性激素的改变在尿路功能障碍的病因及反应中起主要作用。在动物研究中，卵巢切除术（Ovx）会导致平滑肌（SM）无力和萎缩，而补充雌激素可逆转这些影响。我们的研究旨在确定雌激素增加导致收缩力增强的机制。
将20只新西兰雌性白兔分成五组，每组四只。第1组作为对照组，第2 - 5组的兔子接受卵巢切除术，第2组卵巢切除术后未接受雌二醇，第3 - 5组在卵巢切除术后2周开始分别通过皮下缓释片植入给予17-β雌二醇（1毫克/千克/天），持续1、3和7天。在实验期结束时，对每只兔子进行麻醉，然后取出膀胱进行收缩性、组织学和生化研究。
卵巢切除术导致膀胱收缩功能显著降低，而给予雌二醇后测试的膀胱收缩力增强。卵巢切除术导致平滑肌/胶原蛋白比值降低，而雌激素则使其升高。卵巢切除术后雌激素受体（ER）密度显著增加。雌激素治疗1天后，ER密度显著低于对照水平，但在雌激素治疗期间逐渐升高。
本研究表明，补充雌激素介导了一种“功能性肥大”，即一种以对所有形式刺激的收缩反应增加以及平滑肌/胶原蛋白比值增加为特征的肥大。
