Characterization of antiestrogen stimulation of cell number and prolactin production

The antiestrogens LY117018 and tamoxifen increased prolactin production about 4-fold and cell number about 2.5-fold in the pituitary tumor cell line, GH4C1; these increases were 30-40% of the maximal effects of estradiol. The antiestrogens competed with binding of [3H]estradiol, and LY117018 was more active than tamoxifen in biological activities and binding activity. The antiestrogens inhibited stimulation caused by 10(-10) M estradiol; the inhibition could be overcome by increased estradiol concentrations. Tamoxifen and LY117018 increased the amount of prolactin mRNA per cell. These antiestrogens behave as partial agonists in the GH4C1 cells, but have two unusual features. Estrogens are approximately 10-fold more potent in stimulating cell number than in stimulating prolactin production, but the antiestrogens showed the same dose-response for both effects. The partial agonist activity was biphasic and at higher concentrations the antiestrogens showed more antagonist activity (GH4C1 cells, 17 beta-estradiol, tamoxifen).