ANTINIDATORY EFFECT OF LUTEAL-PHASE ADMINISTRATION OF MIFEPRISTONE (RU486) IS ASSOCIATED WITH CHANGES IN ENDOMETRIAL PROSTAGLANDINS DURING THE IMPLANTATION WINDOW
Nr. Nayak et al., ANTINIDATORY EFFECT OF LUTEAL-PHASE ADMINISTRATION OF MIFEPRISTONE (RU486) IS ASSOCIATED WITH CHANGES IN ENDOMETRIAL PROSTAGLANDINS DURING THE IMPLANTATION WINDOW, Contraception, 58(2), 1998, pp. 111-117
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.