Dopamine as a prolactin (PRL) inhibitor.
Dopamine as a prolactin (PRL) inhibitor.
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DOI：
10.1210/edrv.22.6.0451
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发表时间：
2001-12
影响因子：
20.3
通讯作者：
N. Ben-Jonathan;R. Hnasko
中科院分区：
文献类型：
--
作者：
N. Ben-Jonathan;R. Hnasko
多巴胺是一种小而相对简单的分子，具有多种功能。在大脑中，它作为一种经典的神经递质，其衰减或过度活跃可导致帕金森病和精神分裂症等疾病。生物合成酶、转运蛋白和受体的克隆和鉴定的重大进展增加了我们对多巴胺的代谢、释放、再摄取和作用机制的认识。多巴胺通过垂体门静脉血从几个下丘脑神经束到达垂体，下丘脑神经束受PRL本身、雌激素和几种神经肽和神经递质的调节。多巴胺与2型多巴胺受体结合，2型多巴胺受体在功能上与膜通道和G蛋白连接，并抑制垂体催乳素的高内在分泌活性。除了通过控制钙流来抑制PRL释放外，多巴胺还激活几种相互作用的细胞内信号通路并抑制PRL基因表达和催乳素细胞增殖。因此，PRL体内平衡应被视为在一个良好的平衡之间的作用多巴胺作为抑制剂和许多下丘脑，全身和局部因素作为刺激剂，其中没有一个尚未出现作为一个主要的PRL释放因子。转基因动物的产生与过度表达或突变的基因扩大了我们的了解多巴胺-PRL相互作用和生理后果的扰动。PRL在人体中的释放在许多方面与实验室动物不同，受到临床实践中使用的几种药物的影响。高催乳素血症是男性和女性生殖障碍的主要神经内分泌相关原因。高催乳素血症的治疗极大地受益于越来越有效和选择性的多巴胺能药物的产生。
Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical neurotransmitter whose attenuation or overactivity can result in disorders such as Parkinson's disease and schizophrenia. Major advances in the cloning and characterization of biosynthetic enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of dopamine. Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself, estrogens, and several neuropeptides and neurotransmitters. Dopamine binds to type-2 dopamine receptors that are functionally linked to membrane channels and G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling calcium fluxes, dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice. Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs.