Induction of myometrial 11β-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid and protein expression late in rat pregnancy

Peter J. Burton, Arunasalam M. Dharmarajan, Susan Hisheh, Brendan J. Waddell

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22 Citations (Scopus)

Abstract

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 11β-hydroxysteroid dehydrogenase (11βHSD). Therefore, this study examined changes in myometrial 11βHSD bioactivity and expression (messenger RNA and protein) of the 11βHSD-1 isoform and whether 11βHSD-1 and GR are colocalized to myometrial cells. Myometrial 11- oxoreductase activity (conversion of [3H]11-dehydrocorticosterone to [3H]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 11β-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 ± 1%). The marked induction of 11-oxoreductase activity late in pregnancy was strongly and positively correlated with both 11βHSD-1 messenger RNA expression (by Northern analysis) and protein (by Western analysis; r = 0.96 and 0.98, respectively; P < 0.001). Moreover, 11βHSD-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 11βHSD-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 11βHSD-1 serves to enhance local glucocorticoid actions and thus facilitate parturition.

Original languageEnglish
Pages (from-to)5700-5706
Number of pages7
JournalEndocrinology
Volume137
Issue number12
DOIs
Publication statusPublished - 1996

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