IMMUNOLOCALIZATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 ANDTYPE-2 IN RAT UTERUS - VARIATION ACROSS THE ESTROUS-CYCLE AND REGULATION BY ESTROGEN AND PROGESTERONE

Glucocorticoid hormone action in several target tissues is dependent n ot 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 inhib itory effects on a range of important functions, particularly in relat ion 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 H SD-2 immunostaining was localized to endometrial stromal cells and myo metrial cells, with no staining evident in epithelial cells or eosinop hils. Immunostaining for both enzymes was cycle dependent, being maxim al at proestrus and minimal at diestrus. Western blot analysis of whol e uterus at proestrus showed the presence of 34- and 40-kDa immunoreac tive species for 11 beta HSD-1 and -2, respectively. These immunoreact ive signals were almost abolished by ovariectomy, but this effect was reversed for both enzymes by estrogen replacement with or without prog esterone. These effects of ovariectomy and steroid replacement were co nfirmed by immunocytochemical analysis, with the exception that proges terone appeared to enhance the stimulatory effects of estrogen on 11 b eta HSD-2 specifically within the endometrial stroma. In conclusion, t hese results establish the presence of both 11 beta HSD-1 and -2 in th e nonpregnant rat uterus and show distinct distributions for the two e nzymes 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 ea ch 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.