Prostaglandin E2 receptor expression in fetal baboon lung at 0.7 gestation after betamethasone exposure.
The fetal lung produces and metabolizes prostaglandin (PG) E2. In vitro PGE2 induces surfactant production via E prostaglandin (EP)1 and cyclic adenosine monophosphate (cAMP)-coupled EP (EP2 and EP4) receptors. Glucocorticoids alter PG function and increase lung function in preterm neonates. We hypothesized that fetal exposure to maternally administered betamethasone (betaM) enhances fetal lung EP1 and cAMP-coupled EP receptor expression. Pregnant baboons were injected intramuscularly (i.m.) with either betaM (n=7) or saline [control (CTR); n=8] at 0.7 gestation. Fetal lungs were removed at cesarean section 48 h after the first injection. We determined mRNA levels, protein localization and abundance for all four PGE2 receptors by real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. EP receptors were widely distributed in bronchiolar epithelium, bronchiolar smooth muscle, and endothelium and media of blood vessels, but not alveoli. Compared with CTR, betaM exposure resulted in a twofold EP2 mRNA decrease (p<0.05) in male fetuses only. EP1, EP3, and EP4 receptor mRNA levels were unaffected. Western blot analysis showed no alteration in EP receptor protein expression. In summary, this is the first demonstration of the four EP receptors in fetal lung. The only change after 48-h betaM exposure was a gender-specific decrease in EP2 receptor mRNA.
Schmitz
Thomas
T
AP-HP, Maternité Port-Royal, Hopital Cochin, Université René Descartes Paris V, Paris, France.
Cox
Laura A
LA
Li
Cun
C
Levine
Brian A
BA
Ford
Stephen P
SP
McDonald
Thomas J
TJ
Nathanielsz
Peter W
PW
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism*; D048548:Papio cynocephalus / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis / Q000235:genetics*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
D005938:Glucocorticoids; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D001623:Betamethasone