Effect of dexamethasone on fetal lung 15-hydroxy-prostaglandin dehydrogenase: possible mechanism for the prevention of patent ductus arteriosus by maternal dexamethasone therapy.

Prenatal maternal glucocorticoid treatment has been reported to reduce the incidence of patent ductus arteriosus in prematurely born infants. Patency of the ductus arteriosus is thought to be maintained primarily by the vasodilatory effect of PGE2 both in utero and in prematurely born infants, and lung is a major source of PGE2 in fetuses and neonates. 15-Hydroxy-prostaglandin dehydrogenase (15-PGDH) catalyzes the initial reaction in converting biologically active PGE2 to its inactive analogue, 15-keto-PGE2. In the present study, effect of prenatal dexamethasone treatment on the activity of fetal rat lung 15-PGDH was studied at 20, 21 and 22 days of gestation. Activity of fetal lung 15-PGDH more than doubled from 20 to 22 days of gestation. Dexamethasone treatment at 0.4 mg/kg and 0.8 mg/kg significantly increased the activity of 15-PGDH in both 20- and 21-day fetuses but had no effect on 22-day fetuses. We speculate that the clinical observation that prenatal glucocorticoid treatment reduces the incidence of patent ductus arteriosus in premature infants may in part be due to the stimulatory effect of glucocorticoid on the activity of 15-PGDH in fetal and neonatal lung and possibly other organs.