CELLULAR-LOCALIZATION AND DEVELOPMENTAL REGULATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 (11-BETA-HSD1) GENE-EXPRESSION IN THE OVINE PLACENTA

This study was designed to examine the cellular localization and devel opmental regulation of 11 beta-hydroxysteroid dehydrogenase (11 beta-H SD) type 1 gene expression in the ovine placenta. Placental tissues we re collected at discrete times between days 59 and 143 of pregnancy (t erm=145 days). Levels of 11 beta-HSD1 mRNA were determined by Northern blot analysis. The level of both dehydrogenase and reductase activiti es of 11 beta-HSD1 was assessed by a radiometric conversion assay usin g cortisol and cortisone as physiological substrates. The cellular loc alization of 11 beta-HSD1 protein was determined by standard immunohis tochemical technique using a polyclonal antibody specific for the ovin e protein. High levels of 11 beta-HSD1 mRNA were detected in the place nta by day 59, and there was a trend towards a decrease between days 9 8-103 and 125-128 (P=0.06). The level of placental 11 beta-HSD1 mRNA r emained unchanged thereafter. Levels of both 11 beta-HSD1 dehydrogenas e and reductase activities followed a similar pattern except that in b oth cases there was a significant decrease between days 98-103 and 125 -128 (P<0.05). Moreover, under the present assay conditions, the dehyd rogenase activity was always predominant, suggesting that the net effe ct of placental 11 beta-HSD1 activity would lead to glucocorticoid ina ctivation. Thus, the decreased 11 beta-HSD1 activity in the placenta a t days 125-128 was consistent with, and may help to explain, the appar ent increase in the placental transfer of cortisol from mother to fetu s during that time. Throughout pregnancy, intense 11 beta-HSD1 immunor eactivity was detected in fetal trophoblastic cells, maternal stromal cells and blood vessels. In contrast, maternal syncytium was immunoneg ative before day 125, but became immunopositive thereafter. The observ ed predominant direction of 11 beta-HSD1 activity in vitro and its pat tern of localization in the ovine placenta are consistent with the hyp othesis that placental 11P-HSD protects the fetus from adverse effects of maternal glucocorticoids by inactivating glucocorticoids locally. (C) 1997 W. B. Saunders Company Ltd.