title: Effects of estradiol and some antiestrogens (clomiphene, tamoxifen, and hydroxytamoxifen) on luteinizing hormone secretion by rat pituitary cells in culture.
abstract: Primary pituitary cell cultures from adult female rats were incubated for 4 or 24 h with various concentrations of estradiol (E2) or the antiestrogens (AE) tamoxifen (TMX), 4-hydroxytamoxifen (OH-TMX), and clomiphene citrate (CC). The luteinizing hormone (LH)-response of these cultures to gonadotrophin releasing hormone (GnRH) was monitored. Treatment for 4 or 24 h with high concentrations (10(-5) M) of the AE significantly decreased the GnRH-induced LH-release by the gonadotrophs. The negative E2-effect, which is observed in this model after 4 h was enhanced and the positive E2-effect, which occurs after 24 h, was completely reversed into a negative effect by these high AE-concentrations. Treatment of pituitary cells with increasing concentrations of E2 (10(-13)-10(-6) M) or AE (10(-12)-10(-5) M) for 24 h led first to a dose dependent increase of the LH-response to 5 X 10(-10) M GnRH. At higher E2- or AE-concentrations this positive effect was lost, resulting in bell shaped dose-response curves. The following maximal effective concentrations (EDmax) were found: E2 = 10(-10) M, OH-TMX = 10(-9) M, CC = 10(-7) M, TMX = 10(-6) M. Incubation of pituitary cells for 24 h with concentrations of AE near their EDmax and stimulation with increasing concentrations (10(-11)-10(-7) M) of GnRH resulted in significant increases of LH-secretion over a wide range of GnRH-concentrations. It is concluded that AE possess marked intrinsic activities on pituitary LH-secretion: at extremely high concentrations they suppress the GnRH-induced release of the gonadotrophin. At lower concentrations they increase the pituitary LH-response to GnRH in a manner which is qualitatively indistinguishable from that of E2.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002996:Clomiphene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; D002996:Clomiphene; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone