DIFFERENTIAL DEPLETION OF CYTOPLASMIC HIGH AFFINITY OESTROGEN RECEPTORS AFTER THE in vivo ADMINISTRATION OF THE ANTIOESTROGENS, CLOMIPHENE, MER‐25 AND TAMOXIFEN

Abstract

1 The in vivo actions of the oestrogen antagonists, MER-25 and tamoxifen upon the cytosol oestrogen receptors prepared from amygdala, hypothalamus, pituitary and uterus of rats were studied 24 h after drug administration. 2 There was a dose-related depletion of cytosol oestrogen receptors. However, the uterine and pituitary receptors were consistently affected at a lower dose than were those from the brain. 3 The ratios of the combined central ED50 to the combined peripheral ED50 were clomiphene 169 greater than MER-25 19.2 greater than tamoxifen 2.13. 4 The receptor changes were not related to biological activity monitored by serum luteinizing hormone levels and uterotrophic response. 5 The possible role of these drug effects in the induction of ovulation and future developments are discussed.

Follicular Phase Dynamics with Combined Aromatase Inhibitor and Follicle Stimulating Hormone Treatment

“…The overall pregnancy rate was similar in letrozole plus FSH and FSH-only cycles per completed IUI cycle (17.94 vs. 16.87%, respectively, P ϭ 0.8). The cumulative pregnancy rate in group I and group II was 30.05 and 22.04%, respectively ( Table 7).…”

Aromatase inhibitors in ovarian stimulation

“…weeks rather than hours as is the case with natural estrogen. Such extended binding ultimately depletes ER concentrations by interfering with the normal process of ER replenishment [1,2]. The antiestrogenic effect on the hypothalamus and the pituitary, is believed to be the main mechanism of action of CC for ovarian stimulation.…”

Biological activity and steroid receptor interactions of cyclofenil with the oestrogen target tissues of the brain, pituitary gland and uterus of the rat

“…Clomiphene and tamoxifen interact with the cytoplasmic oestrogen receptor of the brain and pituitary gland, but in vivo larger doses are required to affect the hypothalamic oestrogen receptors, access of the drug being prevented by the blood-brain barrier (Ginsburg, MacLusky. Morris & Thomas, 1977;Kurl & Morris, 1978). This paper describes experiments which were performed to see whether the oestrogen antagonist cyclofenil could be shown to interact with the oestrogen receptor system of the brain and pituitary, as well as the uterus, and whether exclusion of the drug from the brain is associated with all the ovulation-inducing antioestrogens.…”