Effect of oestrogen antagonist on hypothalamic oestrogen receptors

Abstract

THE oestrogen antagonist CI-628 can block completely oestrogen-induced sexual receptivity in rats even when the antagonist is given as long as 6 h after oestrogen¹. But as CI-628 does not displace labelled oestradiol from hypothalamic tissue when given at times when it does block the behavioural effects of the oestrogen, the inhibition is not due to simple competitive inhibition. The behavioural inhibition, however, might be due to an inhibition of the action of oestrogen on hypothalamic receptors. This was suggested by the report that oestrogen antagonists can deplete cytoplasmic oestrogen receptors in the uterus², but fail to stimulate production of new receptor, a process which is induced by oestrogen. We have now shown that CI-628 depletes hypothalamic oestrogen receptors, that receptor replenishment occurs very slowly and that CI-628 delays receptor replenishment after oestradiol treatment, suggesting that receptor replenishment might be important for the behavioural effects of oestradiol.