Estrogen and ghrelin decrease cytoplasmic expression of p27kip1, a cellular marker of ageing, in the striated anal sphincter and levator muscle of ovariectomized rats

Abstract

A study was carried out to investigate the effect of estrogen and/or ghrelin on the cellular marker of ageing, p27kip1, in pelvic floor muscles of ovariectomized rats. Virgin Wistar rats (13 months old) underwent ovariectomy followed (1 month) by 42 daily intraperitoneal 17-beta estradiol (10 microg/kg), ghrelin (2 microg/kg), both hormones, or placebo vehicle (n=6x4 groups). Six more age-matched animals underwent sham surgery without ovariectomy. Cytoplasmic expression of p27kip1 in the striated urethral and anal sphincters and levator muscle was measured by Western blot analysis in all animals (n=30). p27kip1 signal intensity significantly increased postovariectomy in all muscles compared to sham animals. In the anal sphincter and levator, signal intensity decreased to sham levels with ghrelin or estrogen and decreased further after estrogen or ghrelin and estrogen/ghrelin administration. Urethral sphincter signal intensity decreased without reaching sham levels after drug administration. Estrogen and/or ghrelin replacement reverses the ovariectomy-induced exacerbation of biochemical cellular ageing in the anal sphincter and levator muscle of middle-aged rats.

Ageing of the female pelvic floor: towards treatment a la carte of the “geripause”

“…This is accompanied by considerable interest in the contemporary biomedical literature, in particular, about the prevalence, detrimental effects, and management of support-related pelvic floor dysfunction (pelvic organ prolapse, urinary incontinence, and fecal incontinence) in the geripausal population. There seems to be no consensus, however, whether the exact underlying mechanism is normative ageing, falling circulating estrogen levels caused by menopausal ovarian failure, or a combination of both factors [3][4][5][6][7][8][9].It is widely believed that estrogen deprivation at the climacteric is primarily responsible for support-related pelvic floor dysfunction in geripausal women. This assumption is based on the detection of estrogen receptors in the components of continence-maintaining and supportive pelvic floor structures in premenopausal women and experimental animals [3][4][5][6].…”

“…There seems to be no consensus, however, whether the exact underlying mechanism is normative ageing, falling circulating estrogen levels caused by menopausal ovarian failure, or a combination of both factors [3][4][5][6][7][8][9].…”

“…This is accompanied by considerable interest in the contemporary biomedical literature, in particular, about the prevalence, detrimental effects, and management of support-related pelvic floor dysfunction (pelvic organ prolapse, urinary incontinence, and fecal incontinence) in the geripausal population. There seems to be no consensus, however, whether the exact underlying mechanism is normative ageing, falling circulating estrogen levels caused by menopausal ovarian failure, or a combination of both factors [3][4][5][6][7][8][9].…”

“…This assumption is based on the detection of estrogen receptors in the components of continence-maintaining and supportive pelvic floor structures in premenopausal women and experimental animals [3][4][5][6]. In turn, estrogen replacement had been extensively used to prevent or restore the decline in pelvic floor support and/or deterioration of urinary and fecal control after the menopause but without critical analysis of the long-term cure rates or evidence-based improvement in clinical outcome after treatment in most studies [7].…”

“…It is not usually appreciated that there are widespread and age-related biological changes, independent of the altered ovarian hormonal milieu of the menopausal transition, that contributes to the adverse chronobiological effects on different tissues in geripausal women [3][4][5][6]. In addition, morphological, physiological, and clinical data indicate that specific "intrinsic" ageing changes in the pelvic floor superimposed on extrinsic estrogen deficiency could be responsible for the decreased integrity observed in geripausal women [3-6, 11, 12].…”