INDUCTION OF MYOMETRIAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 MESSENGER-RIBONUCLEIC-ACID AND PROTEIN EXPRESSION LATE IN RAT PREGNANCY

Myometrial function in pregnancy is regulated by a range of hormonal s timuli, including glucocorticoids, particularly in the period leading up to parturition. Glucocorticoid hormone action is dependent not only on expression of glucocorticoid receptor (GR) within target cells, bu t also on local expression of the enzyme 11 beta-hydroxysteroid dehydr ogenase (11 beta HSD). Therefore, this study examined changes in myome trial 11 beta HSD bioactivity and expression (messenger RNA and protei n) of the 11 beta HSD-1 isoform and whether 11 beta HSD-1 and GR are c olocalized to myometrial cells. Myometrial 11-oxoreductase activity (c onversion of [H-3]11-dehydrocorticosterone to [H-3]corticosterone) was only just detectable (<6%) at the postestrus stage of the cycle and o n days 5 and 10 of pregnancy, but then increased markedly by day 16 (4 5 +/- 2%). This activity increased further to maximal levels on day 22 of pregnancy (55 +/- 3%) and remained high on day 23 (term; 34 +/- 3% ) before decreasing by 24 h postpartum (9 +/- 2%). High 11 beta-dehydr ogenase activity was evident before (87 +/- 1%) and during the first h alf(day 5, 91 +/- 1%; day 10, 88 +/- 2%) of pregnancy, was lower on da ys 16 (55 +/- 2%), 22 (39 +/- 3%), and 23 (58 +/- 1%), then returned t o prepregnancy levels 24 h postpartum (86 ir 1%). The marked induction of 11-oxoreductase activity late in pregnancy was strongly and positi vely correlated with both 11 beta HSD-1 messenger RNA expression (by N orthern analysis) and protein (by Western analysis; r = 0.96 and 0.98, respectively; P < 0.001). Moreover, 11 beta HSD-1 and GR immunoreacti vity were colocalized to the smooth muscle cells of the myometrium and the uterine epithelium late in pregnancy. Collectively, these data de monstrate that a marked induction of 11 beta HSD-1 expression occurs i n the rat myometrium near term, and this is associated with increased 11-oxoreductase bioactivity. As GR is coexpressed in the myometrium, w e suggest that the induction 11 beta HSD-1 serves to enhance local glu cocorticoid actions and thus facilitate parturition.