Cyr M, Morissette M, Landry M, Di Paolo T
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Faculty of Pharmacy, Laval University Quebec, Sainte-Foy, Canada.
Neuroreport. 2001 Mar 5;12(3):535-9. doi: 10.1097/00001756-200103050-00021.
We have previously shown in rats that estradiol has brain regionally specific effects on AMPA receptors. The present study investigated hormonal specificity of AMPA receptors by comparing the effect of estradiol with tamoxifen or raloxifene, which have varying effects on estrogen response in breast, bone and uterus. Ovariectomy in rats decreased uterus weight which was restored by estradiol treatment, whereas tamoxifen and raloxifene had only a weak effect. Ovariectomy left unchanged AMPA receptor specific binding in rat brain whereas estradiol, tamoxifen and raloxifene decreased it in cortical and striatal regions of ovariectomized rats. Hence, tamoxifen and raloxifene showed agonist estrogenic activity on AMPA receptors in specific brain regions, which can be dissociated from their antagonist estrogenic activity in the periphery.
我们之前在大鼠身上已表明，雌二醇对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体具有脑区特异性作用。本研究通过比较雌二醇与他莫昔芬或雷洛昔芬的作用，探究了AMPA受体的激素特异性，他莫昔芬和雷洛昔芬对乳腺、骨骼和子宫的雌激素反应有不同影响。大鼠卵巢切除术后子宫重量减轻，雌二醇治疗可使其恢复，而他莫昔芬和雷洛昔芬的作用较弱。卵巢切除对大鼠脑内AMPA受体特异性结合无影响，而雌二醇、他莫昔芬和雷洛昔芬可降低去卵巢大鼠皮质和纹状体区域的AMPA受体特异性结合。因此，他莫昔芬和雷洛昔芬在特定脑区对AMPA受体表现出雌激素激动活性，这与其在外周的雌激素拮抗活性不同。
