GESTATIONAL-AGE DEPENDENCE OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE AND ITS RELATIONSHIP TO THE ENZYMES OF PHOSPHATIDYLCHOLINE SYNTHESIS IN LUNG AND LIVER OF FETAL-RAT

Increase in fetal surfactant synthesis and lung maturity is caused by the glucocorticoidal induction of enzymes required for phosphatidylcho line (PC) synthesis towards the end of gestation. The regulation of ge stational age-dependent induction of PC synthesis by glucocorticoids i s still unclear. Since 11-beta-hydroxysteroid dehydrogenase (11 beta-H SD) activity and its metabolising capacity for glucocorticoids have be en suggested to play a central role in this regulation, we measured th e gestational age-dependent changes in 11 beta-HSD and PC synthesizing enzymes in lung and liver of fetal rat. The activity of cholinephosph ate cytidyltransferase (CCT; key enzyme in PC synthesis), choline phos photransferase (CPT) and lysolecithin acyltransferase (LAT) were found to increase gradually in the lung towards the end of gestation, reach ed peak values at term followed by a decrease of activity reaching fin ally adult levels. Only CK activity exhibited constant levels until te rm followed by a slight increase after the birth. In comparison with t he lung, the liver enzymes followed a similar pattern, but at a higher rate of activity except for CCT which was higher in the lung. The act ivity of 11 beta-HSD in fetal lung microsomes was detectable from day 20 and increased towards the end of gestation in the lung and liver of the rat. Oxidase activity was always found to exceed the reductase ac tivity. The activity of 11 beta-HSD continued to increase after delive ry and reached peak levels in adult animals in both organs. In order t o test the hypothesis, whether 11 beta-HSD activity and PC synthesis a re induced by increasing endogenous glucocorticoidal levels, we examin ed on day 19 of gestation the effect of dexamethasone (DEXA) on enzyma tic activities (11 beta-HSD, CCT) and on [C-14]choline incorporation i n phosphatidylcholine in fetal lung organoid cultures. Additionally, c hanges in CCT activity in fetal lungs after maternal administration of DEXA were measured. DEXA accelerated 11 beta-HSD and CCT activities a s well as [C-14]choline incorporation. We conclude, that endogenous gl ucocorticoids induce PC synthesis as well as 11 beta-HSD activity in l ung and liver of the fetal rat. Fetal PC synthesis is not altered by i ncreasing 11 beta-HSD levels, because the increase of free serum corti costerone levels apparently exceeds the metabolising capacity of 11 be ta-HSD towards term.