Effect of Estrogen Deprivation on the Expression of Aquaporins and Nitric Oxide Synthases in Rat Vagina
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Estrogen deprivation in rats decreased vaginal secretions, AQP-2, e-NOS, and n-NOS expression, which was restored by estradiol treatment, while AQP-1 expression remained unchanged.
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Abstract
INTRODUCTION: The expression of aquaporin (AQP) water channels in rat vagina was recently reported. AIM: The purposes of this study were to investigate the effect of 17beta-estradiol on the expression of the AQP-1 and AQP-2 water channels and nitric oxide synthase (NOS) isoforms in rat vagina. METHODS: Female Sprague-Dawley rats (230-240 g, N = 90) were divided into three groups: control (N = 30), bilateral ovariectomy (N = 30), and bilateral ovariectomy, followed by subcutaneous injections of 17beta-estradiol (50 microg/kg/day, N = 30). After 4 weeks, genital hemodynamics and vaginal secretions were measured after pelvic nerve stimulation, and the animals were then killed. The expression and cellular localization of AQP-1, AQP-2, endothelial NOS (e-NOS), and neuronal NOS (n-NOS) were determined in each group by immunohistochemistry and Western blot. MAIN OUTCOME MEASURES: The expression and cellular localization of AQPs and NOS isoforms after estrogen deprivation. RESULTS: Estimated vaginal secretions (mg, mean +/- standard error) were significantly lower in the ovariectomized group (2.9 +/- 0.62) than in the control group (5.7 +/- 1.25) and returned to the control value in the group after treatment with 17beta-estradiol (6.5 +/- 1.22) (P < 0.05). Both AQP-1 and e-NOS immunoreactivities were localized in the capillaries and venules of the lamina propria of the vagina, and n-NOS was expressed in the nerve fibers of the subepithelial lamina propria. The expression of AQP-2 was localized solely in the superficial layer of the vaginal epithelium. The protein expressions of AQP-2, e-NOS, and n-NOS were significantly lower after ovariectomy and were restored to the control level after 17beta-estradiol treatment. However, there was no significant change in AQP-1 expression. CONCLUSIONS: Decreased vaginal secretion after estrogen deprivation may be partly due to functional changes in both AQPs and NOS isoforms in the vagina. The potential role of AQPs in water transport in the vagina might differ according to the type of AQP.
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