Immunolocalization of 11 -Hydroxysteroid Dehydrogenase Types 1 and 2 in Rat Uterus: Variation Across the Estrous Cycle and Regulation by Estrogen and Progesterone

Abstract

Glucocorticoid hormone action in several target tissues is dependent not only on the expression of the glucocorticoid receptor, but also on that of the 11β-hydroxysteroid dehydrogenase (11βHSD) enzymes, 11βHSD-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 11βHSD enzymes in the rat uterus at each stage of the estrous cycle and after ovariectomy with or without estrogen/progesterone replacement. In cycling rats 11βHSD-1 was localized to luminal and glandular epithelial cells and to eosinophils in both the endometrial stroma and myometrium. In contrast, 11βHSD-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 11βHSD-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 11βHSD-2 specifically within the endometrial stroma. In conclusion, these results establish the presence of both 11βHSD-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 11βHSD expression will ultimately depend on the reaction direction for each enzyme, but 11βHSD-2 is likely to limit disruptive effects of glucocorticoids on the endometrial stroma, and 11βHSD-1 may then serve to selectively reactivate glucocorticoids in epithelial cells.