| The vagina is a key organ in the peripheral genital arousal response. In animal models, pelvic nerve stimulation increases vaginal wall compliance, blood flow and transudation of fluid. Decreases in ovarian steroids are known to induce structural changes in the vagina, and evidence is mounting that alterations in the hormonal milieu contribute to genital pathophysiology. To date, however, mechanisms by which sex steroids regulate vaginal arousal responses have not been adequately studied. Further, limited data are available on the effects of hormone replacement on tissue morphology, hormone receptor distribution and vaginal innervation. We propose that imbalances in sex steroid hormone levels alter the distribution, expression and actions of steroid receptors and neurotransmitters, leading to structural and functional changes in vaginal tissue and impairment the arousal response. The goal of this study was to assess dynamic changes in vaginal tissue structure with hormone deprivation and administration.; Female Sprague-Dawley rats were used as an animal model. Intact animals served as controls. Ovariectomized animals were treated for a two week period with vehicle, estradiol, testosterone, progesterone, or a combination of estradiol plus testosterone or progesterone. To assess changes in vaginal physiology and morphology, physiological and histological techniques were used, including stereological analysis and immunohistochemistry for localization of hormone receptors and various neuronal markers.; Ovariectomy produced a significant decrease in epithelial height and loss of the epithelial glycogen layer. In addition, estrogen receptor was up-regulated, progesterone receptor was down-regulated, but androgen receptor expression was unaffected. Parallel physiological studies demonstrated a significant decrease in vaginal blood flow. Estradiol replacement restored ovariectomy-induced changes. Interestingly, a subphysiological dose of estradiol resulted in hyperplasia of the vaginal epithelium and non-vascular smooth muscle. Neither testosterone nor progesterone had a significant effect on histological features in ovariectomized animals. Unique effects of testosterone treatment included an increase in androgen receptor density and small adrenergic nerve fibers. Addition of either testosterone or progesterone to estradiol mitigated, but did not abolish the effects of estradiol alone.; This study demonstrates that sex steroid replacement restores the structural and functional integrity of vaginal tissues in ovariectomized animals. Present observations suggest that combined replacement regimens may be required for an optimal physiological response. |
