Inhibition of Estrous Behavior by Progesterone in Rats: Role of Neural Estrogen and Progestin Receptors*

Sexual receptivity can be induced in ovariectomized rats with sequential injections of 17 beta-estradiol-3-benzoate (EB; 2 micrograms sc) and progesterone given 24 h apart. If a high dose of progesterone is used, estrous behavior is followed by a period during which sexual receptivity cannot be reinduced with a second progesterone injection (sequential inhibition). We have examined the effects of a hormone treatment which causes a sequential inhibition on levels of estrogen and progestin receptors in the hypothalamus-preoptic area-septum of ovariectomized rats. In a preliminary experiment, a single injection of 2 micrograms EB caused a significant increase in the concentration of brain cell nuclear estrogen receptors, Peak levels were seen at 12-24 h and remained significantly elevated as long as 72 h after EB. In a second experiment, we found that 48 h after EB, brain cytoplasmic estrogen receptors were significantly depressed and nuclear estrogen receptors were significantly elevated. However, a single progesterone injection (5 mg, sc) 24 h after EB had no significant effect on either cytoplasmic or nuclear estrogen receptor levels. Forty-eight hours after EB, brain cytoplasmic progestin receptors were significantly elevated compared with oil-injected controls. In a third experiment, progesterone (5 mg, sc) given 24 h after EB reduced neural cytoplasmic progestin receptors to levels significantly below those of oil-injected controls at 48 h. These results are consistent with the suggestion that progesterone does not interact with neural estrogen receptors to inhibit lordosis in rats. Rather, we suggest that progesterone may induce a behavioral refractoriness to subsequent progesterone treatments, at least in part, by reducing the concentration of neural cytoplasmic progestin receptors.