Modulation of xanthine dehydrogenase and oxidase activities during the hormonal induction of vaginal epithelial differentiation in ovariectomized mice

Abstract

Abstract The modulation of xanthine dehydrogenase/oxidase (XD/XO) activities in vaginal epithelium as a function of estrogen- and progesterone-induced differentiation was investigated in ovariectomized SENCAR mice. The vaginal epithelium of ovariectomized mice consisted of one or two cell layers. Intraperitoneal administration of 20 μg 17β-estradiol stimulated vaginal hyperplasia, and orthokeratinization. In contrast, although i.p. administration of 2.5 mg progesterone induced hyperplasia, it caused mucification of surface cells. Relative to ovariectomized control mice, vaginal XO specific activities were significantly elevated within 48 h of estradiol treatment and reached a maximum (285%–330% of control) 24–48 h later. The changes in XO specific activity correlated with the appearance of granular and horny layers in the epithelium, and reflected increases in both tissue XD content and the conversion of XD to XO. Approximately 45% of total XD + XO activity was XO in control mice. In contrast, 80% of total activity was contributed by XO in mice 72 h or 96 h after 17β-estradiol treatment. In marked contrast, vaginal XO + XD and XO specific activities, and XO/ XD + XO ratios were unaffected in ovariectomized mice treated with progesterone. Collectively, these studies suggest that the expression of XD, and the conversion of XD to XO in vaginal epithelium are differentiation-specific, and characteristic of the orthokeratinization pathway of differentiation.