Interaction of the anti-estrogen CI-628 and estradiol on plasma LH and hypothalamic LH-RH in the female rat.

The effects of the anti-estrogen Ci-628 have been tested on both plasma LH and hypothalamic LH-RH content in ovariectomized or ovariectomized, estradiol (E2)-implanted rats, in order to correlate those parameters with the [3H]E2 retention in the hypothalamus and the pituitary. Incresing doses of CI-628 induced a dose-dependent inhibition of [3H]E2 retention in both cytosolic and nuclear fractions of the pituitary. In contrast, hypothalamic retention of [3H]E2 is only inhibited significantly with higher doses of CI-628 (2.4 and 24 mg/kg). In ovariectomized rats, only a high dose of CI-628 (24 mg/kg) is able to decrease elevated LH levels observed following castration. In the presence of E2, CI-628 has both estrogenic and anti-estrogenic properties on LH secretion. CI-628 acts at the pituitary level to decrease the tissue sensitivity to LH-RH, but has no effect on mediobasal hypothalamic (MBH) LH-RH content.