Inhibition of brain oestrogen receptors by RU 58668.

The purpose of this study was to determine if injections of the 11 beta-substituted steroidal antioestrogen, RU 58668, would block two measures of oestrogen receptor action in ovariectomized adult female rats. Using an in vitro nuclear exchange assay, it was found that RU 58668 reduced cell nuclear [3H]-oestradiol binding in brain tissue 24 h after it was injected. However, pituitary cell nuclear [3H]-oestradiol binding was significantly reduced just 2 h after the antioestrogen was injected. Our results demonstrate that RU 58668 can reach the brain following a subcutaneous injection, but that it needs more time to reach the brain than it does to reach the pituitary. Since the levels of hypothalamic and pituitary progestin receptors are known to be regulated by oestradiol, cytosolic [3H]-R5020 binding was used as an in vitro assay of endogenous oestrogen receptor action. RU 58668 blocked induction by oestradiol of cytosolic [3H]-R5020 binding in both the brain and pituitary 48 h after it was injected. In the absence of oestradiol, RU 58668 did not stimulate cell nuclear [3H]-oestradiol binding or cytosolic [3H]-R5020 binding in either brain or pituitary. In conclusion, injections of RU 58668 blocked two measures of oestrogen receptor action in the brain and pituitary without showing oestrogenic activity itself.