title: Noradrenergic inhibitors cause accumulation of nuclear progestin receptors in guinea pig hypothalamus.
abstract: A series of experiments was performed to study the possible behavioral relevance of the apparent regulation of hypothalamic cytosol progestin receptors by noradrenergic transmission in female guinea pigs. In the first experiment, ovariectomized guinea pigs were injected with estradiol benzoate followed 36 h later by the dopamine-beta-hydroxylase inhibitor, U-14,624 or vehicle. Twelve h later, they were injected with progesterone and tested hourly for sexual behavior. Six h after the progesterone injection, a time at which inhibition of sexual behavior by the U-14,624 was confirmed, they were killed, and cytosol and nuclear progestin receptors were assayed in the hypothalamus and cerebral cortex. No difference was seen in the concentration of progestin receptors after drug treatment in these animals that also received a progesterone injection. In subsequent experiments, it was found that the U-14,624-inhibition of progesterone-facilitated sexual behavior is not accompanied by an inhibition of nuclear progestin receptor accumulation. Furthermore, it was found that the decreased cytosol progestin receptor level caused by U-14,624 prior to progesterone injection was accompanied by an increase in the concentration of nuclear progestin receptors. The increase in nuclear progestin receptors was also seen after treatment with the alpha-adrenergic antagonist, prazosin, U-14,624 does not compete with [3H]R 5020 for binding to the progestin receptor, suggesting that it does not directly cause translocation of progestin receptors. The results of these experiments suggest that the decrease in the concentration of cytosol progestin receptors caused by noradrenergic inhibitors is not due entirely to an interference with the formation of cytosol progestin receptors. Rather, it seems that these drugs, in some way, also cause the accumulation of progestin receptors in cell nuclei. Furthermore, they suggest that the mechanism by which these drugs inhibit sexual behavior may not be by interference with the progestin receptor system.
authors.forename: J D
authors.initials: JD
authors.lastname: Blaustein
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007031:Hypothalamus / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D010668:Phenylthiazolylthiourea / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D009435:Synaptic Transmission
chemical_list: D011980:Receptors, Progesterone; D010668:Phenylthiazolylthiourea; D011374:Progesterone; D004958:Estradiol; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine; D011224:Prazosin