Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, People's Republic of China.
Gen Comp Endocrinol. 2011 Aug 1;173(1):48-55. doi: 10.1016/j.ygcen.2011.04.024. Epub 2011 May 6.
In many fishes, dopamine (DA) strongly inhibits luteinizing hormone (LH) release by direct action at the pituitary level. In this study, the effect of DA on LH synthesis was examined by detecting its β-subunit mRNA level in immature grass carp pituitary cells. Results showed that DA inhibited LHβ mRNA expression and its inhibition was antagonized by a DA D2 receptor (DRD2) antagonist, sulpiride, suggesting that DA inhibited LH synthesis via DRD2. This notion was further supported by the finding that the grass carp DRD2 (gcDRD2) immunoreactivity was observed in the proximal pars distalis of the pituitary in which gonadotrophs are distributed. Accordingly, a full-length cDNA for DRD2 was cloned from grass carp pituitary and it showed closer phylogenetic relationships to the DA D2 receptors compared with the D3 and D4 or D1-like receptors in other vertebrates. Besides brain, the expression of this receptor in pituitary was revealed by tissue distribution assay, implying the pituitary function of gcDRD2 in immature grass carp. In grass carp pituitary cells, gcDRD2 transcript level was stimulated by DA and this stimulation was blocked by sulpiride. However, hCG, a functional homolog of grass carp LH, was found to inhibit gcDRD2 mRNA expression, indicating an intrapituitary negative feedback of LH on gcDRD2 expression. In view of our observation that the DRD2 mediated the dopaminergic inhibition of LH synthesis, we speculate that the DA stimulation and LH suppression on gcDRD2 may reinforce or attenuate the DA inhibition on LH synthesis, respectively and this regulation of gcDRD2 may at least partially contribute to the steady state levels of LH mRNA in prepubertal grass carp.
在许多鱼类中，多巴胺（DA）通过在垂体水平的直接作用强烈抑制促黄体激素（LH）的释放。在这项研究中，通过检测未成熟草鱼垂体细胞中 LHβ亚基 mRNA 水平来检查 DA 对 LH 合成的影响。结果表明，DA 抑制 LHβ mRNA 表达，其抑制作用被 DA D2 受体（DRD2）拮抗剂舒必利拮抗，表明 DA 通过 DRD2 抑制 LH 合成。这一观点得到了进一步的支持，即发现草鱼 DRD2（gcDRD2）免疫反应性存在于垂体的近侧部，其中分布有促性腺激素细胞。因此，从草鱼垂体中克隆了全长的 DRD2 cDNA，它与其他脊椎动物的 DA D3 和 D4 或 D1 样受体相比，与 DA D2 受体的系统发育关系更为密切。除了大脑，组织分布测定显示该受体在垂体中的表达，暗示 gcDRD2 在未成熟草鱼中的垂体功能。在草鱼垂体细胞中，DA 刺激 gcDRD2 转录本水平，而舒必利阻断这种刺激。然而，发现草鱼 LH 的功能同源物 hCG 抑制 gcDRD2 mRNA 表达，表明 LH 对 gcDRD2 表达的垂体内负反馈。鉴于我们观察到 DRD2 介导了多巴胺对 LH 合成的抑制作用，我们推测 DA 刺激和 LH 对 gcDRD2 的抑制可能分别增强或减弱 DA 对 LH 合成的抑制，并且这种 gcDRD2 的调节至少部分有助于青春期前草鱼 LH mRNA 的稳定水平。
