Low dose RU486 prevents progesterone antagonism on uterine growth and concomitant type II oestradiol binding induction by oestradiol in rats.
The effect of RU486, a synthetic antisteroid, on the antagonism of progesterone (Pg) and dexamethasone (Dex) against oestradiol (Oe) induced uterine growth, and on uterine oestradiol binding (type I and type II sites) was studied in ovariectomized CFY rats. Changes of hypothalamic low affinity [3H]Oe binding have also been evaluated. Inhibitory effects of Pg but not of Dex on uterine growth and type II Oe binding site induction were prevented by RU486. Antiprogestin effect of RU486 could also be demonstrated on low affinity [3H]Oe binding in hypothalami. The inhibitory effect of dexamethasone on type II Oe binding was not opposed by antisteroid, on the contrary, RU486 seemed to potentiate this effect of Dex. Evaluation of type I binding was complicated by the distorting effect of type II binding at the saturation curve. Changes of type I binding seemed to parallel those of type II binding except after Oe+Dex treatment where an increased level of uterine cytoplasmic type I sites and a simultaneous decrease of type II sites were found. Blockage of [3H]Oe binding at high RU486 concentrations was found in vitro in the uterine cytoplasmic fraction. A less pronounced effect was observed in the nuclear fraction. Possible mechanisms of the RU486 effect on type II Oe binding are discussed.
Garai
J
J
Department of Pathophysiology, University Medical School, Pécs, Hungary.
Vértes
M
M
Kovàcs
S
S
D000818:Animals; D001665:Binding Sites; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone