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 phosphatidylcholine (PC) synthesis towards the end of gestation. The regulation of gestational age-dependent induction of PC synthesis by glucocorticoids is still unclear. Since 11-beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity and its metabolising capacity for glucocorticoids have been suggested to play a central role in this regulation, we measured the gestational age-dependent changes in 11 beta-HSD and PC synthesizing enzymes in lung and liver of fetal rat. The activity of cholinephosphate cytidyltransferase (CCT; key enzyme in PC synthesis), choline phosphotransferase (CPT) and lysolecithin acyltransferase (LAT) were found to increase gradually in the lung towards the end of gestation, reached peak values at term followed by a decrease of activity reaching finally adult levels. Only CK activity exhibited constant levels until term followed by a slight increase after the birth. In comparison with the 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 activity 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 activity. The activity of 11 beta-HSD continued to increase after delivery and reached peak levels in adult animals in both organs. In order to test the hypothesis, whether 11 beta-HSD activity and PC synthesis are induced by increasing endogenous glucocorticoidal levels, we examined on day 19 of gestation the effect of dexamethasone (DEXA) on enzymatic activities (11 beta-HSD, CCT) and on [14C]choline incorporation in phosphatidylcholine in fetal lung organoid cultures. Additionally, changes in CCT activity in fetal lungs after maternal administration of DEXA were measured. DEXA accelerated 11 beta-HSD and CCT activities as well as [14C]choline incorporation. We conclude, that endogenous glucocorticoids induce PC synthesis as well as 11 beta-HSD activity in lung and liver of the fetal rat. Fetal PC synthesis is not altered by increasing 11 beta-HSD levels, because the increase of free serum corticosterone levels apparently exceeds the metabolising capacity of 11 beta-HSD towards term.
Hundertmark
S
S
Department of Obstetrics and Gynaecology, Klinikum Steglitz, Freie Universität Berlin, Germany.
Ragosch
V
V
Schein
B
B
Bühler
H
H
Lorenz
U
U
Fromm
M
M
Weitzel
H K
HK
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000032:analysis; D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D002250:Carbon Radioisotopes; D002794:Choline / Q000378:metabolism; D002797:Choline Kinase / Q000032:analysis; D019916:Choline-Phosphate Cytidylyltransferase; D003907:Dexamethasone / Q000494:pharmacology; D002798:Diacylglycerol Cholinephosphotransferase / Q000032:analysis; D005333:Fetus / Q000201:enzymology; D005865:Gestational Age; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008099:Liver / Q000196:embryology* / Q000201:enzymology; D008168:Lung / Q000196:embryology* / Q000201:enzymology; D009713:Nucleotidyltransferases / Q000032:analysis; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D002250:Carbon Radioisotopes; D010713:Phosphatidylcholines; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D002797:Choline Kinase; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D002794:Choline