INTERCONVERSION OF CORTISOL AND CORTISONE IN THE BABOON PLACENTA AT MIDGESTATION - EXPRESSION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1 MESSENGER-RNA

At midgestation in the baboon, 11 beta-hydroxysteroid dehydrogenase (1 1 beta-HSD) catalysed interconversion of cortisol (F) and cortisone (E ) during transuterine passage favors the formation of F. Because the s ite(s) of oxidation/reduction of F and E are not clear, the present st udy compared F-E interconversion in placenta, decidua and chorion in v itro. In addition, because the reduction of E to F is catalysed only b y the 11 beta-HSD-1, we also determined whether the mRNA for this enzy me was expressed in baboon placenta, including placental syncytiotroph oblast cells; the site of fetal-maternal exchange. Placentas were obta ined on day 100 of gestation (term = day 184) and villous tissue, deci dua and chorion isolated, minced in HBSS and incubated (300-400 mg) in duplicate for 0.1-24 h in Medium 199 containing 10% fetal bovine seru m and [H-3]F and [C-14]E. Radiolabelled F and E were purified from inc ubates and the percentage conversion of F to E and E to F was calculat ed. In decidua, mean (+/- SE; n = 3) conversion of E to F (69 +/- 2%) was greater than oxidation of F to E (26 +/- 2%). Conversion of E to F in placenta (50 +/- 1%) and chorion (39 +/- 9%) was also extensive an d greater than or equal to that for the oxidation of F to E (39 +/- 4% and 32 +/- 4%, respectively). The apparent ratio of 11 beta-HSD reduc tive/oxidative activity was maintained when respective tissues from fo ur baboons were incubated for 18 h with or without 4.4 mu M excess rad ioinert substrate. Expression of 11 beta-HSD-1 mRNA was determined by Northern blot by hybridization of poly (A)+-enriched RNA from tissues obtained at midgestation with [P-32]labelled human 11 beta-HSD-1 cDNA. This cDNA hybridized to a single mRNA species of 1.6 kb in decidua, w hole placental villous tissue and syncytiotrophoblast cells, but not t o RNA isolated from fetal baboon kidney. The results of the present st udy demonstrate that at midgestation in the baboon, 11 beta-HSD activi ty in intact placenta and decidua in vitro favored the formation off f rom E, presumably catalysed by the 11 beta-HSD-1 enzyme protein, the m RNA for which is present in placental syncytiotrophoblasts. Moreover, based on overall mass and extensive vascularity, we suggest that the n et formation of F from E during transuterine passage in vivo at this s tage of gestation results from the 11 beta-HSD-1 in the syncytiotropho blast cells of the baboon placenta. Copyright (C) 1996 Elsevier Scienc e Ltd.