RUI: Receptor Mediation of Antiestrogen Effects

虽然人们早就知道雌激素对生殖生理和行为有深远的影响，但这种类固醇激素也会改变摄食行为、体重增加和脂质代谢。据信，雌激素的这些广泛作用是通过受体依赖过程介导的。特异性蛋白受体定位于大脑不同区域的靶细胞中，干扰类固醇受体结合活性的化合物会减弱激素反应。事实上，这些化合物，也被称为抗雌激素，是阐明雌激素作用机制的极好工具。一个非常有趣的发现是，这些合成制剂部分或完全拮抗雌激素对生殖生理和行为的影响，但模仿雌激素对调节过程的影响，如摄食。格雷博士将检查受体系统，通过这些抗雌激素发挥其雌激素激动与拮抗作用。她已经证明在不同的大脑区域存在两种特定的抗雌激素结合位点。她现在将描述中枢神经系统中抗雌激素结合位点的分布和结合特性。这些研究的结果应该能让我们更好地理解雌激素是如何对生殖和调节系统产生复杂影响的。此外，抗雌激素药物，如他莫昔芬、萘氧化胺、克罗米芬，被广泛用于治疗雌激素依赖性乳腺肿瘤。她在受体介导抗雌激素作用方面的工作可能有助于我们理解这些化合物是如何在肿瘤细胞中作为生长抑制剂的。

While estrogens have long been known to have profound effects on reproductive physiology and behavior, this steroid hormone also alters feeding behavior, body weight gain and lipid metabolism. It is believed that these wide range of effects of estrogens are mediated through a receptor-dependent process. Specific protein receptors are localized in target cells within distinct brain regions and compounds that interfere with steroid- receptor binding activity attenuates the hormone response. Indeed these compounds, also known as antiestrogens, are an excellent tool for elucidating the mechanisms underlying the action of estrogen. An extremely interesting finding is that these synthetic agents partially or fully antagonize the effects of estrogen on reproductive physiology and behavior but mimic the effects of estrogen on regulatory processes, such as feeding. Dr. Gray will examine the receptor systems by which these antiestrogens exert their estrogenic agonistic vs antagonistic effects. She has demonstrated the presence of two specific antiestrogen binding sites in different brain regions. She will now characterize the distribution and binding properties of antiestrogen binding sites in the CNS. The results from these studies should lead to a better understanding of how estrogen exerts its complex effects on both reproductive and regulatory systems. Moreover, antiestrogens, such as tamoxifen, nafoxidine, clomiphene, are widely used for the treatment of estrogen- dependent breast tumors. Her work on receptor mediation of antiestrogen effects may help us understand how these compounds act as growth suppressants in tumor cells.