Simard J, Labrie F
Mol Cell Endocrinol. 1985 Feb;39(2):141-4. doi: 10.1016/0303-7207(85)90131-5.
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.
雌激素可增加培养的大鼠垂体前叶细胞基础状态下以及促性腺激素释放激素（LHRH）诱导的促黄体生成素（LH）释放。在用1 nM 17β-雌二醇预孵育48小时后，对LHRH的最大LH反应增加了1.5倍，而LHRH作用的半数有效浓度（ED50）值从500 pM降至200 pM，降低了2.5倍。17β-雌二醇对0.3 nM LHRH诱导的LH释放的最大3倍刺激作用在解离常数（KD）值为14.4 pM时发挥。他莫昔芬（300 nM）完全阻断了高达1 nM的17β-雌二醇的强效刺激作用，1 nM是所用雌激素的最高浓度。如分别在7.7 nM和34 nM的半数抑制浓度（IC50）值下他莫昔芬完全逆转0.1 nM和1.0 nM 17β-雌二醇的刺激作用所示，抗雌激素在雌激素结合位点与17β-雌二醇竞争性相互作用。单独存在时，他莫昔芬无雌激素活性。目前的数据表明，他莫昔芬在大鼠垂体促性腺细胞中对LHRH诱导的LH释放控制方面表现为纯抗雌激素作用。
