TISSUE-SPECIFIC MESSENGER-RIBONUCLEIC-ACID EXPRESSION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 AND TYPE-2 AND THE GLUCOCORTICOID RECEPTOR WITHIN RAT PLACENTA SUGGESTS EXQUISITE LOCAL-CONTROL OF GLUCOCORTICOID ACTION

Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates transplacental passage of maternal glucocorticoids to the fetus and i s thus a key determinant of fetal glucocorticoid levels. It has also b een proposed that placental 11 beta-HSD expression may influence local glucocorticoid actions by regulating access of corticosterone to the glucocorticoid receptor (GR) or mineralocorticoid receptor (MR). There fore, tile present study used a rat model to assess whether the GR or MR are coexpressed with the two forms of 11 beta-HSD (types 1 and 2) i n the placental labyrinth zone, the major site of maternal-fetal trans fer, and in the basal zone, the primary site of placental hormone synt hesis. In, situ hybridization analysis was used to assess messenger RN A (mRNA) expression for the GR, MR, 11 beta-HSD-1, and 11 beta-HSD-2 i n the two placental zones on days 16, 19 and 22 of pregnancy (term = d ay 23). Whereas expression of the GR appeared relatively unchanged in both zones at these three stages of pregnancy, that of 11 beta-HSD-1 c learly increased in the labyrinth zone but fell in basal zone, iyherea s the opposite pattern of expression was observed for 11 beta-HSD-2. M R expression was not detected at any stage. The pattern of placental 1 1 beta-HSD-2 mRNA expression over days 16, 19, and 22 of pregnancy was paralleled by changes in 11 beta-HSD-2-specific bioactivity, but desp ite clear expression of 11 beta-HSD-1 mRNA, no bioactivity attributabl e to this enzyme was measurable in either placental zone. To assess th e role of fetal adrenal maturation on these changes in 11 beta-HSD, tw o experimental models, maternal adrenalectomy and fetectomy, were empl oyed. Maternal adrenalectomy on day 13 advanced maturation of the feta l adrenal cortex but had no effect on 11 beta-HSD-2 bioactivity in eit her of the placental zones at day 19. Placental 11 beta-HSD-2 bioactiv ity on day 22 was also unaffected by fetectomy 3 or 6 days earlier. In conclusion, the consistent expression of the GR in the two placental zones late in pregnancy suggests that concomitant and marked changes i n 11 beta-HSD-1 and 11 beta-HSD-2 expression could have a major influe nce on glucocorticoid action in the placenta at this time. Moreover, t he changes in 11 beta-HSD expression appear to be unrelated to develop ment of the fetal adrenal cortex and are likely to reduce the placenta l glucocorticoid barrier near the end of pregnancy.