MRC Brain Metabolism Unit, University Department of Pharmacology, 1 George Square, Edinburgh, EH8 9JZ, Scotland.
Mol Cell Neurosci. 1993 Feb;4(1):83-92. doi: 10.1006/mcne.1993.1010.
The aim of the present study was to determine the effect of estradiol-17beta, in its positive feedback mode for the release of prolactin and luteinizing hormone (LH), on gene expression of 5-hydroxytryptamine (5-HT) and dopamine receptors. Gene expression was determined by measurement of the levels of receptor mRNA by in situ hybridization in brain sections from adult female rats. The animals were ovariectomized under halothane anesthesia on the morning of diestrus, given a sc injection of either estradiol benzoate (EB) or oil (vehicle), and killed between 1600-1700 h of the next day, presumptive proestrus. The injection of EB in this preparation is known to stimulate a massive surge of LH and prolactin in the late afternoon of presumptive proestrus. The injection of EB produced a significant increase in silver grain densities representing 5-HT(2) receptor mRNA in the dorsal raphe nucleus (DRN) and a significant reduction in these grain densities in the medial septum and diagonal band of Broca. The number of cells expressing 5-HT(2) receptor mRNA was increased by 290% in the DRN and decreased by 25% in the medial preoptic area. Estradiol had no effect on silver grain densities, or numbers or percentages of cells expressing 5-HT(2) receptor mRNA in any of the other nine brain regions or choroid plexus studied, and had no effect on the levels of 5-HT(1A), 5-HT(1C), D(1), or D(2) receptor mRNA in any region studied. These data suggest that the 5-HT(2) receptor is a key receptor involved in mediating the positive feedback stimulation by estradiol-17beta of LH and prolactin release. Since estradiol increases 5-HT levels in the DRN, the data raise the intriguing possibility that estrogen positive feedback on LH and prolactin release is mediated by a feed-forward 5-HT drive which results in increased 5-HT release at DRN-derived nerve terminals on hypothalamic neurons which control LH and prolactin release.
本研究旨在确定雌二醇-17β（E2）在促黄体生成素（LH）和催乳素释放的正反馈模式下对 5-羟色胺（5-HT）和多巴胺受体基因表达的影响。通过原位杂交测量脑切片中受体 mRNA 的水平来确定基因表达，这些脑切片来自于处于发情间期的成年雌性大鼠。在发情间期的上午，大鼠在氟烷麻醉下进行卵巢切除术，然后分别接受苯甲酸雌二醇（EB）或油（载体）的 sc 注射，并于第二天 1600-1700 小时之间，即假定发情前期被杀死。在这种制剂中，EB 的注射已知会在假定发情前期的下午晚些时候刺激 LH 和催乳素的大量激增。EB 的注射导致背侧中缝核（DRN）中 5-HT（2）受体 mRNA 的银颗粒密度显著增加，而中隔和 Broca 斜带中的这些颗粒密度则显著降低。DRN 中表达 5-HT（2）受体 mRNA 的细胞数量增加了 290％，而在视前内侧区中则减少了 25％。E2 对任何其他 9 个脑区或脉络丛中 5-HT（2）受体 mRNA 的银颗粒密度、细胞数量或百分比均没有影响，也没有影响任何研究区域中 5-HT（1A）、5-HT（1C）、D（1）或 D（2）受体 mRNA 的水平。这些数据表明，5-HT（2）受体是参与介导雌二醇-17β对 LH 和催乳素释放的正反馈刺激的关键受体。由于 E2 增加了 DRN 中的 5-HT 水平，因此这些数据提出了一个有趣的可能性，即雌二醇对 LH 和催乳素释放的正反馈是通过 5-HT 驱动的前馈来介导的，该驱动导致 DRN 衍生的神经末梢在控制 LH 和催乳素释放的下丘脑神经元上增加 5-HT 释放。
