Competition of Phenothiazines with Oestradiol for Oestradiol Receptors in Rat Brain

3H-Oestradiol uptake by the median eminence, anterior pituitary, and uterus of ovariectomized albino rats is significantly reduced when the hormone is injected after i.v. administration of perphenazine, while its uptake in the cerebral cortex is not affected by perphenazine. The most pronounced competition is noted 30 min after the oestradiol injection: it lasts 60 min in the median eminence, but more than 2 h in the anterior pituitary, where the 3H-oestradiol uptake is 10 times higher. The peak of 3H-oestradiol radioactivity in the different organs is reached in the median eminence and cerebral cortex 15 min after injection, in the anterior pituitary after 2 h, and in the uterus more than 3 h afterwards. A decline in the 3H-oestradiol uptake is observed in the median eminence; but in the anterior pituitary it rises steadily for up to 2 h. Increasing the perphenazine-priming dose yields a dose-response curve of decreased 3H-oestradiol uptake. The fact that aminopromazine and phenothiazine are also able to partly saturate the binding receptors of oestradiol in its target-organs points to specific receptor competition. This may explain some of the central endocrine effects exerted by phenothiazines.