Fondazione IRCCS Policlinico Mangiagalli Regina Elena, Unit of Endocrinology and Diabetology, Milan, Italy.
Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):43-53. doi: 10.1517/17425250903352501.
Dopamine-agonists are the treatment of choice of prolactin-secreting pituitary adenomas (PRL-omas). Their actions on D2 dopamine receptor (DRD2) and the clinical outcome may be affected by polymorphisms.
PRL-omas are well-differentiated endocrine tumors expressing DRD2. The dopamine-agonist cabergoline (CB), normalizes prolactin and reduces tumor size in about 80 - 90% of patients. DRD2 polymorphisms correlate with neuropsychiatric disorders, in particular alcoholism and schizophrenia. This review describes the DRD2 polymorphisms, their functional effects, and their impact on susceptibility and response to dopamine-agonists treatment. Searching PubMed database for pertinent articles we found that some DRD2 polymorphisms, particularly TaqIA, TaqIB and NcoI, are associated with different receptor binding in brain areas. One study carried out in patients with PRL-omas found a correlation between NcoI and TaqIA and resistance to CB. In particular, resistant patients had higher prevalence of NcoI-T allele than the responsive patients, while the commonest haplotype (having TaqIA2 allele) was associated with better response.
This review deals with the connection between DRD2 polymorphisms and PRL-oma treatment and suggests hypotheses for further studies.
Only one study was carried out to analyze the role of DRD2 polymorphisms in PRLomas response to CB. Further studies, including pituitary and hypothalamus in vivo determination of DRD2 binding according to DRD2 genotypes, investigation of possible post-receptorial mechanisms involved, as well as population studies in collaboration with psychiatrists and neurologists, are needed.
多巴胺激动剂是催乳素分泌性垂体腺瘤（PRL-omas）的首选治疗方法。它们对多巴胺 D2 受体（DRD2）的作用及其临床结果可能受到多态性的影响。
PRL-omas 是分化良好的内分泌肿瘤，表达 DRD2。多巴胺激动剂卡麦角林（CB）可使催乳素正常化，并使约 80-90%的患者肿瘤缩小。DRD2 多态性与神经精神障碍相关，特别是酒精中毒和精神分裂症。这篇综述描述了 DRD2 多态性、它们的功能影响，以及它们对多巴胺激动剂治疗易感性和反应的影响。我们在 PubMed 数据库中搜索了相关文章，发现一些 DRD2 多态性，特别是 TaqIA、TaqIB 和 NcoI，与大脑区域的不同受体结合有关。一项对 PRL-omas 患者进行的研究发现，NcoI 和 TaqIA 与 CB 耐药性之间存在相关性。特别是，耐药患者的 NcoI-T 等位基因的患病率高于敏感患者，而最常见的单倍型（具有 TaqIA2 等位基因）与更好的反应相关。
本篇综述涉及 DRD2 多态性与 PRL-oma 治疗之间的联系，并提出了进一步研究的假设。
仅有一项研究旨在分析 DRD2 多态性在 PRLomas 对 CB 反应中的作用。需要进一步的研究，包括根据 DRD2 基因型对垂体和下丘脑进行 DRD2 结合的体内测定，研究可能涉及的受体后机制，以及与精神科医生和神经科医生合作进行的人群研究。
