Cyr M, Landry M, Di Paolo T
Oncology and Molecular Endocrinology Research Center and Faculté de Pharmacie, Université Laval, Sainte-Foy, Québec, Canada.
Neuropsychopharmacology. 2000 Jul;23(1):69-78. doi: 10.1016/S0893-133X(00)00085-3.
Hormonal specificity of modulation of brain 5-HT(2A) receptors was investigated by comparing activity of compounds with varying effects on estrogen response in breast, bone, and uterus. A two-week estradiol treatment stimulated the decreased uterine weight of ovariectomized rats to intact rat values whereas an increase of 29% with tamoxifen and 16% with raloxifene was observed compared to vehicle-treated ovariectomized rats. In 18 assayed brain regions, ovariectomy decreased 5-HT(2A) receptor binding and mRNA levels in anterior cingulate and frontal cortices, striatum, and nucleus accumbens; estradiol restored this decrease to intact rat values. Dehydroepiandrosterone (DHEA) increased ovariectomized rats 5-HT(2A) receptor expression only in striatum and cortical amygdala. Tamoxifen increased 5-HT(2A) receptor density only in striatum. Raloxifene, an uterine estrogen receptor (ER) antagonist, increased, like estradiol, 5-HT(2A) receptor density and expression in cingulate and frontal cortices, striatum, and nucleus accumbens. Brain regional specificity of estradiol, DHEA, tamoxifen, and raloxifene on 5-HT(2A) receptors was observed which can be dissociated from peripheral activity.
通过比较对乳腺、骨骼和子宫中雌激素反应有不同影响的化合物的活性，研究了大脑5-HT(2A)受体调节的激素特异性。为期两周的雌二醇治疗可使去卵巢大鼠降低的子宫重量恢复到完整大鼠的水平，而与溶剂处理的去卵巢大鼠相比，他莫昔芬可使其增加29%，雷洛昔芬可使其增加16%。在18个检测的脑区中，去卵巢会降低前扣带回、额叶皮质、纹状体和伏隔核中5-HT(2A)受体的结合及mRNA水平；雌二醇可将这种降低恢复到完整大鼠的水平。脱氢表雄酮（DHEA）仅在纹状体和皮质杏仁核中增加去卵巢大鼠的5-HT(2A)受体表达。他莫昔芬仅在纹状体中增加5-HT(2A)受体密度。雷洛昔芬是一种子宫雌激素受体（ER）拮抗剂，与雌二醇一样，可增加扣带回、额叶皮质、纹状体和伏隔核中5-HT(2A)受体的密度和表达。观察到雌二醇、DHEA、他莫昔芬和雷洛昔芬对5-HT(2A)受体的脑区特异性，且这种特异性可与外周活性分离。
