Estrogen-dependent estrous behavior in rabbits is antagonized by the antiprogestin RU486.

ABSTRACT

Estrogen receptor-alpha (ERα) dimerizes with unliganded progesterone receptor (PR) in target tissues to trigger genomic and non-genomic effects. In ovariectomized rats the antiprogestin RU486 or antisense nucleotides against PR antagonize estradiol-induced sexual receptivity. We determined the relevance of unliganded PR for the expression of estrogen-dependent scent-marking (chinning) and sexual receptivity by injecting RU486 to a) ovariectomized (ovx) rabbits given estradiol benzoate (EB; 5µg/day); b) intact rabbits. Chinning and lordosis were quantified in ovx animals before (5days; baseline) and during hormonal treatments EB+RU486 (20mg/day; n=18) or EB+vehicle (n=18). On treatment day 4 LQ (lordosis quotient) increased in both groups, relative to baseline (mean±se) LQ=1±5 (baseline) vs 25±21 (EB+RU486) and 2±6 (baseline) vs 37±29 (EB+vehicle). On day 9 LQ values were 22±23 (EB+RU486) and 54±39 (EB+vehicle). Chinning increased only in the EB+vehicle group (day 9=55±46 vs baseline=17±20 marks/10min). In intact rabbits one RU486 injection reduced the LQ from 72±7to 36±8 five hrs later, increased the latency to receive first ejaculation from 45 to 98s, and decreased the number of ejaculations received in the test from 3 to 2 but did not modify mounting latency or chinning. Results support a participation of unliganded PR for the induction (ovx) and maintenance (intact) of rabbit estrous behavior by estrogens.