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 stimuli, 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, but also on local expression of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Therefore, this study examined changes in myometrial 11 beta HSD bioactivity and expression (messenger RNA and protein) of the 11 beta HSD-1 isoform and whether 11 beta HSD-1 and GR are colocalized to myometrial cells. Myometrial 11-oxoreductase activity (conversion of [H-3]11-dehydrocorticosterone to [H-3]corticosterone) was only just detectable (<6%) at the postestrus stage of the cycle and on days 5 and 10 of pregnancy, but then increased markedly by day 16 (45 +/- 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-dehydrogenase activity was evident before (87 +/- 1%) and during the first half(day 5, 91 +/- 1%; day 10, 88 +/- 2%) of pregnancy, was lower on days 16 (55 +/- 2%), 22 (39 +/- 3%), and 23 (58 +/- 1%), then returned to prepregnancy levels 24 h postpartum (86 ir 1%). The marked induction of 11-oxoreductase activity late in pregnancy was strongly and positively correlated with both 11 beta HSD-1 messenger RNA expression (by Northern analysis) and protein (by Western analysis; r = 0.96 and 0.98, respectively; P < 0.001). Moreover, 11 beta HSD-1 and GR immunoreactivity were colocalized to the smooth muscle cells of the myometrium and the uterine epithelium late in pregnancy. Collectively, these data demonstrate that a marked induction of 11 beta HSD-1 expression occurs in the rat myometrium near term, and this is associated with increased 11-oxoreductase bioactivity. As GR is coexpressed in the myometrium, we suggest that the induction 11 beta HSD-1 serves to enhance local glucocorticoid actions and thus facilitate parturition.