Pelvic floor sex steroid hormone receptors, distribution and expression in pre‐ and postmenopausal stress urinary incontinent women

Abstract

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.