Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium

Besides being an antiprogestin, mifepristone (RU 486) was recently shown to antagonize oestrogen-dependent growth in the endometrium, To explore the m olecular mechanisms for this phenomenon, we investigated whether or not the morphological effects of mifepristone are mediated by the progesterone rec eptor (PR) and whether mifepristone has disparate effects on the glandular epithelium and stroma, Six groups of hypogonadal, oestrogen-primed cynomolg us monkeys were treated for 2 weeks with: vehicle only (group I); mifeprist one (group II); mifepristone plus progesterone at 0.2 mg/kg (group III), 1. 0 mg/kg (group ni) or 5.0 mg/kg (group V); and progesterone only (5.0 mg/kg ) (group vn) Histomorphological evaluation showed strikingly compacted stro ma in the mifepristone-exposed endometria (group II), which was partially r eversible by additional progesterone treatment (groups III-V), Glandular pr oliferation (pseudostratification, glandular mitoses) in mifepristone-treat ed monkeys was not significantly different from that in vehicle (oestradiol )-treated monkeys, but was inhibited by progesterone-only treatment. Cells containing vacuoles were scarce in the mifepristone-exposed endometrium, bu t detected frequently in progesterone-exposed endometria, indicating the st rong antisecretory effect of mifepristone on glands. We conclude that oestr ogen-dependent oedema in the stroma is antagonized by mifepristone. The rev ersal of this effect by progesterone suggests a PR-mediated mechanism. In g lands, mifepristone is antiprogestogenic, but not antioestrogenic, Thus, st romal cells may be the target of antiprogestin-induced inhibition of oedema and endometrial growth.