Nuclear Progestin Receptors in Guinea Pig Brain Measured by anin VitroExchange Assay after Hormonal Treatments that Affect Lordosis*

Abstract

An assay was developed for the measurement of progestin receptors in purified cell nuclei of the central nervous system after progesterone injection. The affinity of the nuclear progestin receptor in the hypothalamus-preoptic area-septum of female guinea pigs for [³H]17α,21-dimethyl-19-nor-pregna-4,9- diene-3,20-dione (K_d ≧ 0.16 nm) is similar to that previously reported for the cytosol receptor in this tissue. Although all brain areas studied (hypothalamus, preoptic area-septum, midbrain, and cerebral cortex) accumulated some nuclear progestin receptor after progesterone injection, the hypothalamus had the highest concentration. Guinea pigs primed with a large dose (10 μg) of estradiol benzoate accumulated more nuclear progestin receptor after an injection of progesterone than animals primed with a low dose (1.6 μg) of estradiol benzoate. This is consistent with our previous finding that estradiol benzoate induces cytoplasmic progestin receptors in a dose-dependent manner. By 2–4 h after progesterone injection (0.5 mg) in estrogen-primed guinea pigs, the concentration of nuclear progestin receptors in the hypothalamus-preoptic area-septum peaked as did plasma levels of progesterone. There was a concurrent depletion of progestin receptors from the cytoplasm. By 24 h after progesterone injection, there was no longer any accumulation of nuclear progestin receptors, and the level of cytoplasmic progestin receptors remained low. A second progesterone injection at this time resulted in a 61% lower concentration of nuclear progestin receptors than animals that had received only oil vehicle 24 h earlier. The results are consistent with the notion that the neural progestin receptor system is involved in progesterone’s effects on lordosis in guinea pigs. (Endocrinology106: 1061, 1980)