Cellular localization and developmental regulation of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) gene expression in the ovine placenta

Abstract

Listen

Translate article

This study was designed to examine the cellular localization and developmental regulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 gene expression in the ovine placenta. Placental tissues were collected at discrete times between days 59 and 143 of pregnancy (term=145 days). Levels of 11β-HSD1 mRNA were determined by Northern blot analysis. The level of both dehydrogenase and reductase activities of 11β-HSD1 was assessed by a radiometric conversion assay using cortisol and cortisone as physiological substrates. The cellular localization of 11β-HSD 1 protein was determined by standard immunohistochemical technique using a polyclonal antibody specific for the ovine protein. High levels of 11β-HSD1 mRNA were detected in the placenta by day 59, and there was a trend towards a decrease between days 98–103 and 125–128 ( P=0.06). The level of placental 11β-HSD1 mRNA remained unchanged thereafter. Levels of both 11β-HSD1 dehydrogenase and reductase activities followed a similar pattern except that in both cases there was a significant decrease between days 98–103 and 125–128 ( P < 0.05). Moreover, under the present assay conditions, the dehydrogenase activity was always predominant, suggesting that the net effect of placental 11β-HSD1 activity would lead to glucocorticoid inactivation. Thus, the decreased 11β-HSD1 activity in the placenta at days 125–128 was consistent with, and may help to explain, the apparent increase in the placental transfer of cortisol from mother to fetus during that time. Throughout pregnancy, intense 11β-HSD1 immunoreactivity was detected in fetal trophoblastic cells, maternal stromal cells and blood vessels. In contrast, maternal syncytium was immunonegative before day 125, but became immunopositive thereafter. The observed predominant direction of 11β-HSD1 activity in vitro and its pattern of localization in the ovine placenta are consistent with the hypothesis that placental 110-HSD protects the fetus from adverse effects of maternal glucocorticoids by inactivating glucocorticoids locally.