Söderberg Marie Westergren, Johansson Bengt, Masironi Britt, Byström Birgitta, Falconer Christian, Sahlin Lena, Ordeberg Gunvor Ekman
Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Acta Obstet Gynecol Scand. 2007;86(11):1377-84. doi: 10.1080/00016340701625446.
Hormonal influence on stress urinary incontinence (SUI) is under debate. Sex steroid hormonal activity is mediated by nuclear receptor proteins. The aim of this study is to identify receptor isoforms and their genetic expression in the pelvic floor extra cellular matrix (ECM), and to compare women with and without SUI before and after menopause.
Sub-mucosal para-urethral biopsies from 4 pre-menopausal and 8 postmenopausal patients with SUI were analysed immunohistochemically regarding estrogen receptors (ER) alpha and beta, the progesterone receptor (PR) (A+B) and B, and the androgen receptor (AR). Six pre-menopausal and 5 postmenopausal women served as controls. All receptors were scored manually. Additionally, ER-alpha and ER-beta were quantified by image analysis. Biopsies from 7 pre-menopausal and 7 postmenopausal women suffering from SUI were studied by real-time RT-PCR for expression of ER-alpha, ER-beta, PR and AR. The control group consisted of 5 pre-menopausal and 5 postmenopausal women.
Immunohistochemistry revealed receptor-positive cells for all isoforms in all groups. Higher ER-beta scores were seen in the pre-menopausal SUI group compared to controls. Lower PR-B scores were found after menopause in both groups. The image analysis confirmed that ER-beta was significantly increased in the pre-menopausal SUI group compared to controls (p=0.02). By real-time RT-PCR, no difference of mRNA expression regarding any receptor was detected between any SUI and control group. ER-beta mRNA levels were low or undetectable. There was a significant down-regulation of PR among postmenopausal women (p=0.001).
The para-urethral ECM is a target for sex steroid hormones mediated by the respective receptor. The significant higher expression of ER-beta protein in the pre-menopausal SUI-group was not reflected by a corresponding up-regulation of mRNA which was poorly expressed in all groups.
激素对压力性尿失禁（SUI）的影响仍存在争议。性甾体激素活性由核受体蛋白介导。本研究旨在鉴定盆底细胞外基质（ECM）中的受体亚型及其基因表达，并比较绝经前后有和没有SUI的女性。
对4名绝经前和8名绝经后SUI患者的尿道旁黏膜下活检组织进行免疫组织化学分析，检测雌激素受体（ER）α和β、孕激素受体（PR）（A+B）和B以及雄激素受体（AR）。6名绝经前和5名绝经后女性作为对照。所有受体均进行手动评分。此外，通过图像分析对ER-α和ER-β进行定量。对7名绝经前和7名绝经后SUI女性的活检组织进行实时RT-PCR研究，以检测ER-α、ER-β、PR和AR的表达。对照组由5名绝经前和5名绝经后女性组成。
免疫组织化学显示所有组中所有亚型均有受体阳性细胞。绝经前SUI组的ER-β评分高于对照组。两组绝经后PR-B评分均较低。图像分析证实，绝经前SUI组的ER-β明显高于对照组（p=0.02）。通过实时RT-PCR，在任何SUI组和对照组之间未检测到任何受体的mRNA表达差异。ER-β mRNA水平较低或无法检测到。绝经后女性的PR有显著下调（p=0.001）。
尿道旁ECM是由相应受体介导的性甾体激素的作用靶点。绝经前SUI组中ER-β蛋白的显著高表达并未反映在mRNA的相应上调上，mRNA在所有组中表达均较差。
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