RU-486 ACTION AFTER ESTROGEN PRIMING IN THE ENDOMETRIUM AND OVIDUCTS OF RHESUS-MONKEYS (MACACA-MULATTA)

Recently, we reported that in rhesus monkeys, RU 486 treatment could i nhibit the ability of estradiol (E(2)) to stimulate endometrial regene ration without inhibiting E(2)-dependent oviductal regeneration. In th at work, RU 486 had been administered at the end of an artificial lute al phase when the oviducts were regressed, the endometrium was in a la te secretory state, and estrogen and progestin receptors (ER and PR, r espectively) were at minimal levels in both organs. In the current wor k, we administered RU 486 after 2 weeks of estrogen priming when the o viducts were fully differentiated, the endometrium was in a proliferat ive state, and ER and PR levels were maximal. Our goal was to determin e whether the degree to which RU 486 inhibited E(2) action in either o rgan varied depending on their initial state. Spayed rhesus monkeys we re primed with E(2) for 2 weeks and then treated in four different way s for an additional 2 weeks as follows: I) E(2); II) E(2) plus P; III) E(2), P, and RU 486; and IV) E(2) plus RU 486. Menstruation was not i nduced by any of the four treatments. In group I, continuous treatment with E(2) maintained a typical proliferative endometrium with abundan t Ki-67-positive cells, low levels of apoptosis, and elevated ER and P R; the oviducts were also maintained in a fully ciliated-secretory sta te. In group II, P induced a typical progestational secretory state in the endometrium, with few proliferating (Ki-67-positive) epithelial c ells, undetectable apoptosis, and decreased ER and PR; as expected, th e oviducts were fully regressed, with few Ki-67-positive or ciliated e pithelial cells and low levels of ER and PR, In the endometria of monk eys treated with RU 486 and E(2), either with (group III) or without ( group IV) P, the effects of E(2) on wet weight, thickness, and epithel ial proliferation were more dramatically inhibited than in our previou s study. However, the oviducts of the RU 486-treated animals had remai ned in a hypertrophied, fully ciliated-secretory state as in our previ ous study, with elevated ER and nuclear PR, although epithelial prolif eration was suppressed. The degree to which RU 486 can inhibit estroge n-dependent growth in the endometrium can apparently be affected by th e state of differentiation and/or steroid receptor level at the time t he antiprogestin treatment is begun, but this effect is not evident in the oviduct, which shows only modest antiproliferative effects of the RU 486 treatment.