Zonal distribution of 11β-hydroxysteroid dehydrogenase types 1 and 2 messenger ribonucleic acid expression in the rat placenta and decidua during late pregnancy

Abstract

Glucocorticoid action in several target tissues is dependent on expression of 11β-hydroxysteroid dehydrogenase (11β-HSD), and in the placenta 11β-HSD is thought to regulate transfer of active glucocorticoid to the fetus. This study compared expression of the two recognized 11β-HSD enzymes, types 1 and 2, in the rat placenta and decidua on Days 16 and 22 of gestation (term = Day 23). According to S1 nuclease protection analysis, although mRNA for 11β-HSD-1 was only just detectable in the labyrinth zone on Day 16, by Day 22 this expression had increased almost 20-fold. There was also an increase (approximately 2-fold) in 11β-HSD-1 mRNA in the basal zone between Days 16 and 22. In Day 16 decidua, 11β-HSD-1 mRNA was also highly expressed, but insufficient tissue was available for analysis on Day 22. Western blot analysis showed that immunoreactive 11β-HSD-1 (molecular mass 34 kDa) was present in those tissues with the highest 11β-HSD-1 mRNA expression (Day 16 decidua and Day 22 labyrinth zone). With respect to mRNA for 11β-HSD-2, high expression was observed in the decidua and labyrinth zone at Day 16, but in the latter this expression then declined 90% by Day 22. In contrast, expression of mRNA for 11β-HSD-2 increased more than 3- fold in the basal zone over the same period. Consistent with coexpression of the two 11β-HSD enzymes, both 11-oxoreductase and 11β-dehydrogenase bioactivity were clearly evident in all tissues, and each varied with stage of gestation. Specifically, 11β-dehydrogenase activity in the basal zone increased from 38 ± 2% (mean ± SEM) on Day 16 to 56 ± 2% on Day 22, while 11-oxoreductase activity fell from 55 ± 3% to 43 ± 2% over the same period. In contrast, 11β-dehydrogenase activity in the labyrinth zone fell with advancing pregnancy (Day 16:63 ± 2%; Day 22: 48 ± 2%). Both 11-oxoreductase (58 ± 3%) and 11β-dehydrogenase (38 ± 4%) activities were also evident in decidua at Day 16. In conclusion, this study shows that expression of 11β- HSD-1 and -2 is zone-specific in the placenta and maternal decidua. Moreover, opposite changes in the expression of the two enzymes occur in the basal and labyrinth zones of the placenta over the last days of pregnancy, indicative of distinct regulatory mechanisms and functional significance for the enzymes in the two placental zones.