Maintenance of progesterone-facilitated sexual behavior in female rats requires continued hypothalamic protein synthesis and nuclear progestin receptor occupation.

The role of ongoing progesterone-directed protein synthesis and hypothalamic cell nuclear progestin receptor occupation in maintaining the duration of the period of sexual receptivity was determined in ovariectomized rats treated with 500 micrograms progesterone 44 h after receiving 2 micrograms estradiol benzoate. Injection of the protein synthesis inhibitor anisomycin (100 mg/kg BW) either 2 or 10 h after progesterone treatment resulted in decreased levels of both receptive and proceptive sexual behavior. Similarly, injection of RU 486, an antiprogestin, 2, 6, or 10 h after progesterone injection resulted in inhibition of sexual behavior within 4-8 h after administration. Using a modified cell nuclear isolation technique for the exchange assay of nuclear-bound progestin receptors, elevated levels of progestin binding in hypothalamic cell nuclear fractions were detected as late as 14 h after progesterone injection. By 18 h after progesterone injection, nuclear progestin receptor levels had returned to baseline, a time when the period of sexual behavior had terminated in similarly treated animals. These data suggest that continued progesterone action in hypothalamic cell nuclei is required for the maintenance of progesterone-facilitated sexual behavior in the female rat. Furthermore, they suggest that progesterone action maintains sexual responsiveness by altering the synthesis of a short-lived protein or set of proteins.