Nuclear Progestin Receptors in Rat Brain and Pituitary

Abstract
Progestin receptors in rat brain and pituitary cell nuclei were measured with an in vitro exchange assay in order to examine the role of estrogen priming and of endogenous and exogenous progesterone in determining the amount of receptor which reaches the nuclear compartment. Progesterone administration causes progestin receptors, demonstrable by exchange, to appear in the cell nuclear fraction from rat pituitary, hypothalamus-preoptic area (HYP-POA), and cerebral cortex, all of which contain cytosol progestin receptor sites. The amount of progestin receptor translocated to nuclei by 1 mg of progesterone increases after estrogen priming in pituitary and HYP-POA, tissues which contain progestin receptors inducible by estradiol. The increase in nuclear progestin receptors after progesterone is proportionally the same in estrogen-primed and in unprimed HYP-POA as well as in the cerebral cortex, where noninducible progestin receptors are found. Further characterization of nuclear progestin receptors reveals that those translocated to cell nuclei are differentialy extracted by 0.4 M KCl and that high estrogen treatment in the absence of progesterone appears to give rise to some progestin receptor translocation to nuclei. The influence of both estrogen priming and progesterone release is evident in HYP-POA and pituitary cell nuclei assay by progestin exchange from rats killed at various stages of the estrous cycle. The amount of nuclear progestin receptor increases from diestrus to noon on proestrus, due apparently to endogenous estrogen priming, since progesterone levels remain the same and cytosol progestin receptors are known to increase in this time. Nuclear progestin receptors increase from noon to 16:30 h on proestrus in parallel with the proestrus rise of progesterone. This increase precedes the normal appearance of estrous behavior on the evening of proestrus. When estrogen-primed ovariectomized rats are given varying doses of progesterone and tested for sexual behavior or killed for progestin receptor exchange assays, nuclear progestin receptors are found to increase in the same way as the dose dependence of proceptive sexual behavior. Thus, the translocation of progestin receptors to MBH-POA cell nuclei may be an important step in the activation of proceptive sexual behavior by progesterone.