Somponpun Suwit, Sladek Celia D
Department of Physiology and Biophysics, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Endocrinology. 2002 Aug;143(8):2899-904. doi: 10.1210/endo.143.8.8946.
In rats, the magnocellular neurons that produce vasopressin (VP) and oxytocin (OT) express estrogen receptor-beta (ER-beta). Physiological concentrations of estrogen (E2) inhibit N-methyl-D-aspartate (NMDA)-stimulated VP and OT release from explants of the hypothalamo-neurohypophyseal system (HNS). To determine whether ER-beta mediates inhibition by E2, HNS explants were perifused with and without NMDA (50 microM) in the presence of E2 (50 pg/ml), E2 coupled to BSA (E2:BSA), genistein (100 nM, a phytoestrogen with affinity for ER-beta), or tetrahydrochrysene-R,R,-enantiomer (R,R-THC, a ligand that acts as an agonist on ER-alpha but an antagonist on ER-beta). VP and OT released into the perifusate were measured by RIA. E2 and genistein inhibited NMDA-stimulated VP release, but E2:BSA and R,R,THC were not effective inhibitors. However, R,R,THC blocked E2 inhibition of NMDA-stimulated VP release. The inability of E2:BSA to mimic the effect of E2 indicates that E2 inhibition is not mediated by membrane receptors. The ability of genistein to mimic the effect of E2 suggests that the effect is mediated by ERbeta. This interpretation is supported by the ability of R,R,THC to block but not to mimic the effect of E2. Thus, E2 inhibition of NMDA-stimulated VP and OT release may be mediated by ER-beta.
在大鼠中，产生加压素（VP）和催产素（OT）的大细胞神经元表达雌激素受体β（ER-β）。生理浓度的雌激素（E2）可抑制下丘脑-神经垂体系统（HNS）外植体中N-甲基-D-天冬氨酸（NMDA）刺激的VP和OT释放。为了确定ER-β是否介导E2的抑制作用，在存在E2（50 pg/ml）、与牛血清白蛋白偶联的E2（E2:BSA）、染料木黄酮（100 nM，一种对ER-β具有亲和力的植物雌激素）或四氢 Chrysene-R,R-对映体（R,R-THC，一种对ER-α起激动剂作用但对ER-β起拮抗剂作用的配体）的情况下，对HNS外植体进行有无NMDA（50 μM）的灌流。通过放射免疫分析测定释放到灌流液中的VP和OT。E2和染料木黄酮抑制NMDA刺激的VP释放，但E2:BSA和R,R,THC不是有效的抑制剂。然而，R,R,THC阻断了E2对NMDA刺激的VP释放的抑制作用。E2:BSA无法模拟E2的作用表明E2的抑制作用不是由膜受体介导的。染料木黄酮能够模拟E2的作用表明该作用是由ERβ介导的。R,R,THC能够阻断但不能模拟E2的作用支持了这一解释。因此，E2对NMDA刺激 的VP和OT释放的抑制作用可能是由ER-β介导的。
