Inhibition of sexual behavior in female guinea pigs by a progestin receptor antagonist.

The new steroidal progestin receptor antagonist, RU 38486, was used to determine if progesterone-facilitation of sexual behavior in female guinea pigs requires interaction of the hormone with neural progestin receptors. Five milligrams but not 0.5 mg RU 38486 inhibits the expression of sexual behavior in ovariectomized, estrogen-primed guinea pigs treated with 0.1 mg progesterone. This inhibition can be overcome by administration of a large dose of progesterone, suggesting that the drug-effect is specific to the progestin receptor system. RU 38486 binds, in vitro, to progestin receptors and decreases the availability of hypothalamic progestin receptors in estrogen-treated guinea pigs. These studies provide strong evidence that progesterone interaction with intracellular neural progestin receptors mediates the facilitation of sexual behavior by progesterone in female guinea pigs.