Effects of estradiol and some antiestrogens (Clomiphene, tamoxifen, and hydroxytamoxifen) on luteinizing hormone secretion by rat pituitary cells in culture

Publisher Website
Google Scholar
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 24h with high concentrations (10−5M) of the AE significantly decreased the GnRH-induced LH-release by the gonadotrophs. The negative E2-effect, which is observed in this model after 4h was enhanced and the positive E2-effect, which occurs after 24h, was completely reversed into a negative effect by these high AE-concentrations. Treatment of pituitary cells with increasing concentrations of E2 (10−13–10−6M) or AE (10−12–10−5M) for 24h led first to a dose dependent increase of the LH-response to 5 × 10−10M 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 = 10−10M, OH-TMX = 10−9M, CC = 10−7M, TMX = 10−6M. Incubation of pituitary cells for 24h with concentrations of AE near their EDmax and stimulation with increasing concentrations (10−11–10−7M) 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.

This publication has 23 references indexed in Scilit: