Antepartum glucocorticoid therapy suppresses human placental xenobiotic and steroid metabolizing enzymes.
We investigated the effects of maternal gestational corticosteroid therapy on placental xenobiotic and steroid metabolizing enzymes at term in 20 glucocorticoid/betamethasone treated (with various doses) and control (n=10) women. A single dose of betamethasone (12 mg i.m. twice at a 24-h interval) was given to 15 mothers at risk of preterm delivery to prevent respiratory syndrome in their premature newborns. Five mothers were treated more than once. The gestation time in mothers receiving the glucocorticoid therapy varied from 22-38 gestational weeks. Compared with controls, a significant decrease in placental aromatase activity (53.6+/-18.0 pmol/mg/min versus 119+/-30 pmol/mg/min, P=0.0007) and placental CYP19 mRNA content (by 50 per cent ) was observed in mothers treated with glucocorticoids. Also the formation of androstenedione (13.2+/-8.1 pmol/mg/min, steroids versus 30.03+/-5.2 pmol/mg/min, controls, P< 0.001), using testosterone as the substrate, and 7-ethoxycoumarin O-deethylase (P< 0.05) and 7-ethoxyresorufin O-deethylase (P< 0.09) were slightly decreased in the glucocorticoid treated compared to control patients' values. The changes were not dependent on the number of treatments or the time between treatment and delivery. Our results demonstrate that even a single dose of glucocorticoid given to expectant mothers is associated with diminished placental steroid hormone and xenobiotic metabolizing enzymes at term. Further studies are needed to assess whether these changes affect the well-being of the fetus and its later development.
Paakki
P
P
Department of Pharmacology and Toxicology, University of Oulu, Helsinki, Finland.
Kirkinen
P
P
Helin
H
H
Pelkonen
O
O
Raunio
H
H
Pasanen
M
M
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007752:Obstetric Labor, Premature / Q000188:drug therapy; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000517:prevention & control; D013256:Steroids / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
D005938:Glucocorticoids; D012333:RNA, Messenger; D013256:Steroids; D015262:Xenobiotics; D003907:Dexamethasone; D015660:7-Alkoxycoumarin O-Dealkylase; D001141:Aromatase; D019363:Cytochrome P-450 CYP1A1