Keoxifene shows pure antiestrogenic activity in pituitary gonadotrophs.
Estrogens increase both basal and LHRH-induced LH release in rat anterior pituitary cells in culture. Following 48 h of preincubation with 1 nM 17 beta-estradiol, the maximal LH response to LHRH is increased 1.5-fold while the ED50 value of LHRH action is decreased 2.5-fold from 500 to 200 pM. The maximal 3-fold stimulation of 0.3 nM LHRH-induced LH release by 17 beta-estradiol is exerted at a KD value of 14.4 pM. Keoxifene (300 nM) completely blocks the potent stimulatory effect of 17 beta-estradiol up to 1 nM, the highest concentration of the estrogen used. As shown by the complete reversal of the stimulatory effect of 0.1 and 1.0 nM 17 beta-estradiol by keoxifene at IC50 values of 7.7 and 34 nM respectively, the antiestrogen interacts competitively with 17 beta-estradiol at the estrogen binding site. When present alone, keoxifene shows no estrogenic activity. The present data show that keoxifene acts as a pure antiestrogen on the control of LHRH-induced LH release in rat pituitary gonadotrophs.
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D020849:Raloxifene Hydrochloride; D051381:Rats; D011919:Rats, Inbred Strains
D004965:Estrogen Antagonists; D010880:Piperidines; D007987:Gonadotropin-Releasing Hormone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D007986:Luteinizing Hormone