Maternal selective cyclooxygenase-2 inhibition suppresses estrogen alpha receptor transcripts in the pregnant rabbit uterus

ALPHA RECEPTOR TRANSCRIPTS IN THE PREGNANT RABBIT UTERUS WILBERT FORTSON JR, KAY BEHARRY, NICOLE HAUSMAN, JOSHUA WALTZMAN, STEPHEN NAGEOTTE, TAMEROU ASRAT, University of California, Irvine, Maternal Fetal Medicine, Irvine, California, University of California, Irvine, Pediatrics, Orange, California, U.C. Irvine Medical Center, Long Beach, California, Long Beach Memorial Medical Center, Obstetrics and Gynecology, Long Beach, California, Long Beach Memorial Medical Center, Maternal Fetal Medicine, Orange, California, University of California, Irvine, Obstetrics & Gynecology, Orange, California OBJECTIVE: Parturition is associated with decreased progesterone receptor (PR) responsiveness and estrogen receptor (ER)-a activation in the myometrium. Inducible cyclooxygenase (COX)-2 is principally enzyme involved in parturition, andmay be regulated by estrogen and progesterone.We examinedwhetherCOX-2 inhibition would influence mRNA expression of PR and ER in the uterus from non-laboring pregnant rabbits at term. STUDY DESIGN: Three groups of timed pregnant New Zealand rabbits at 13 days gestation (term = 32 days) were examined. Group 1 was administered celecoxib in suspension (30 mg/kg/day, equivalent to 200 mg BID in humans) in a mixture of 0.5% methylcellulose and 0.1% polysorbate 80 in water (vehicle) by gavage, from 13 to 20 days gestation (Cel-A); Group 2 received celecoxib from 13 to 28 days gestation (Cel-B); and Group 3 (control) received equivalent volume vehicle from 13 to 28 days gestation. At 29 days gestation, the rabbits underwent aseptic cesarean section. Uterine samples were collected and analyzed for PRA/B, PRB, and ERa mRNA expression. PRA was calculated as the difference between PRA/B and PRB. Data was normalized using GAPDH mRNA. RESULTS: Uterine PRA was reduced only in the Cel-A group (ANOVA, P ! .05). ERamRNA expression was reduced 2-fold in the Cel-A and Cel-B groups (P ! .05). PRB mRNA expression remained comparable among the groups. CONCLUSION: We have demonstrated a link between COX-2 and ERa mRNA expression in the non-laboring pregnant rabbit uterus at term. This finding requires further investigation to determine it’s clinical implication. SMFM Abstracts S133