INHIBITION OF RAT SEXUAL-BEHAVIOR BY ANTISENSE OLIGONUCLEOTIDES TO THE PROGESTERONE-RECEPTOR

To test further the idea that sexual behavior in rodents is mediated v ia the progesterone receptor (PR) in the ventromedial nucleus of the h ypothalamus, antisense and sense oligonucleotides to progesterone rece ptor were administered intracerebroventricularly into the third cerebr al ventricle of ovariectomized estrogen-primed animals. Progesterone-f acilitated sexual behavior was inhibited in animals treated with antis ense oligonucleotides, with preceptive and receptive responses being m inimal or completely suppressed. Sexual behavior was not altered by co ntrol sense oligonucleotides. In vitro binding assays of the cytosol p rogesterone receptors demonstrated a 52.2% reduction of PRs in the hyp othalamus of animals that received antisense oligonucleotides, suggest ing a reduction in PR synthesis. These data suggest that a threshold l evel of estrogen-induced hypothalamic PR is critical in the regulation of progesterone-facilitated sexual behavior in female rats.