Immunolocalization of 11β-hydroxysteroid dehydrogenase types 1 and 2 in rat uterus:: Variation across the estrous cycle and regulation by estrogen and progesterone

Glucocorticoid hormone action in several target tissues is dependent not only on the expression of the glucocorticoid receptor, but also on that of the 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) enzymes, 11 beta HSD-1 and -2. In the uterus, glucocorticoids can exert inhibitory effects on a range of important functions, particularly in relation to the effects of estrogen. Therefore, the present study examined immunolocalization of the two 11 beta HSD enzymes in the rat uterus at each stage of the estrous cycle and after ovariectomy with or without estrogen/progesterone replacement. In cycling rats 11 beta HSD-1 was localized to luminal and glandular epithelial cells and to eosinophils in both the endometrial stroma and myometrium. In contrast, 11 beta HSD-2 immunostaining was localized to endometrial stromal cells and myometrial cells, with no staining evident in epithelial cells or eosinophils. Immunostaining for both enzymes was cycle dependent, being maximal at proestrus and minimal at diestrus. Western blot analysis of whole uterus at proestrus showed the presence of 34- and 40-kDa immunoreactive species for 11 beta HSD-1 and -2, respectively. These immunoreactive signals were almost abolished by ovariectomy, but this effect was reversed for both enzymes by estrogen replacement with or without progesterone. These effects of ovariectomy and steroid replacement were confirmed by immunocytochemical analysis, with the exception that progesterone appeared to enhance the stimulatory effects of estrogen on 11 beta HSD-2 specifically within the endometrial stroma. In conclusion, these results establish the presence of both 11 beta HSD-1 and -2 in the nonpregnant rat uterus and show distinct distributions for the two enzymes and cyclic variation related to positive regulation by ovarian steroids. The physiological implications of these patterns of 11 beta HSD expression will ultimately depend on the reaction direction for each enzyme, but 11 beta HSD-2 is likely to limit disruptive effects of glucocorticoids on the endometrial stroma, and 11 beta HSD-1 may then serve to selectively reactivate glucocorticoids in epithelial cells.