Combined estrogen and ghrelin administration decreases expression of p27kip1 and proportion of isomyosin type I in the striated urethral and anal sphincters and levator ani of old ovariectomized rats

Abstract

We compared estrogen and/or ghrelin effects on pelvic floor muscles in old versus young adult ovariectomized rats. Ovariectomized Fisher 344 rats (18 and 3 months old, n = 24 x 2) received 42 daily intraperitoneal 17-beta estradiol (10 microg kg(-1)), ghrelin (2 microg kg(-1)), both, or vehicle (n = 6 x 4/group). Cytoplasmic p27(kip1) expression and isomyosin I proportion in striated urethral and anal sphincters and levator ani were measured, respectively, by Western blot analysis and gel electrophoresis with immunohistochemistry of muscle ghrelin receptors and radioimmunoassay of circulating growth hormone. In young adult rats, estrogen significantly decreased cytoplasmic p27(kip1) and isomyosin I signal intensities. In old rats, ghrelin and estrogen/ghrelin significantly decreased both intensities with greater estrogen/ghrelin effect. Ghrelin receptors were not immunostained in any muscle. Estrogen and/or ghrelin significantly increased or decreased, respectively, circulating growth hormone in old and young adult rats. Estrogen/ghrelin administration reversed pelvic floor muscle ageing changes in old ovariectomized rats through growth hormone production.

Eu-estrogenemia, WHI, timing and the “geripause”

“…However, estrogen plus ghrelin maintained pelvic striated muscle integrity in young rats, but not in elderly ovariectomized rats. Rizk suggests that a timing factor is present and notes, "…the present data further support our conclusion that estrogen deficiency exacerbates the underlying adverse effects of ageing on the striated pelvic floor muscle" [9].…”

“…Rizk et al [9] evaluated estrogen and ghrelin administration in ovariectomized rats. Older rats did not respond to estrogen replacement as well as younger rats.…”

“…1 Eu-estrogenemia and the estrogenic milieus of the woman's life (adapted from [10]). Concentration of estrogen [E] on the abscissa, years on the ordinate (x-axis); P Pregnancy; M menopause; R re-estrogenization; G geripause; dotted line eu-estrogenemia after ovarian failure maintain striated muscle of the proper composition in the pelvic floor [9,11].…”

Aging of Pelvic Floor in Animal Models: A Sistematic Review of Literature on the Role of the Extracellular Matrix in the Development of Pelvic Floor Prolapse

“…As demonstrated by Rizk et al (49), ovariectomy significantly exacerbates urogenital aging changes in rats. Furthermore, in old rats estrogen/ghrelin administration reversed pelvic floor aging changes in ovariectomized rats (50).…”