ANTINIDATORY EFFECT OF LUTEAL-PHASE ADMINISTRATION OF MIFEPRISTONE (RU486) IS ASSOCIATED WITH CHANGES IN ENDOMETRIAL PROSTAGLANDINS DURING THE IMPLANTATION WINDOW

Luteal phase administration of mifepristone provides a significant deg ree of pregnancy protection to monkeys and women. Among several propos ed mediators of the antinidatory action of luteal phase mifepristone, prostaglandins (PG) at the endometrial level appear important, and was examined in the present study using the rhesus monkey as the primate model. To this end, the concentrations of PGE(2) and PGF(2 alpha) in e ndometrium and the profiles of cyclooxygenase (COX) and 15-hydroxy pro staglandin dehydrogenase (PGDH) were examined in untreated control ani mals, in animals subjected to mifepristone treatment (2 mg/day) alone or along with diclofenac (25 mg/day), or along with a PGE(1) analog (1 00 mu g misoprostol), in animals subjected to diclofenac alone treatme nt, and in animals treated with misoprostol alone on cycle days 16, 17 , and 18. Tissue samples were collected on day 20 of treatment cycles from animals with discernible corpora lutea. Early luteal phase treatm ent with diclofenac did not result in any remarkable change in endomet rial prostaglandin concentrations, however, there was an increase in t he profile of COX. Animals exposed to misoprostol in the prereceptive stage, on the other hand, exhibited decreased expression of endometria l COX. The concentrations of PGF(2 alpha) and PGE(2), as well as the r atios of PGF(2 alpha) to PGE(2) concentrations, were increased along w ith a decrease in COX and PGD in endometrial samples following luteal phase mifepristone treatment. Although the underlying cellular mechani sm of regulation of COX and PGDH in mifepistone-treated endometrium re mains to be examined, the decrease in PG catabolism through low PGDH m ay contribute to the increased PG and high ratio of PGF(2 alpha) to PG E(2) in mifepristone-exposed endometrium. it is plausible that mifepri stone action on endometrial cells is mediated by an altered ratio of P GF(2 alpha) to PGE(2). Furthermore, it appears that the regulation of PG milieu by COX and PGDH activities in reproductive tissues is under complex regulatory mechanism and is temporarily correlated with specif ic developmental events. (C) 1998 Elsevier Science Inc. All rights res erved.