垂体腺瘤中多巴胺D_2受体的研究进展

The Progress in Dopamine D_2 Receptor in Pituitary Adenomas

多巴胺(dopamine,DA)是中枢神经系统内最主要的儿茶酚胺类神经递质,在中枢和外周神经系统中都担当了十分重要的作用。DA和其受体的发现引发了神经、临床精神病学的重大突破。正常垂体的前叶和中叶组织中,都存在一定水平的D2受体表达,它们介导了多巴胺对泌乳素(prolactin,PRL)和促黑色素细胞素等激素分泌的负调节作用。D2受体在PRL型垂体腺瘤中存在高表达,在对PRL型垂体腺瘤的治疗中,D2受体激动剂获得了良好的临床效果,目前已成为大多数泌乳素型腺瘤首选的治疗方法。随着分子生物学和放射医学技术的发展,对多巴胺D2受体分子的研究取得了长足的进步。除了PRL型腺瘤外,在相当一部分的非 PRL型腺瘤-包括生长激素型和促性腺激素型和无功能性垂体腺瘤等疾病中,都检测到D2受体的表达,D2受体激动剂的治疗效果得到了深入的探讨和分析。D2受体不同亚型的表达水平也得到进一步的检测,其发挥作用的分子机制也受到关注。D2受体不同亚型的表达水平与D2受体激动剂治疗敏感性之间的联系值得进一步关注。虽然在一些具体的研究结果上,在报道中还存在差异和争论,但有理由相信:随着对D2受体和其亚型分子结构的深入了解,以及相关药物开发的不断完善,D2受体激动剂将在垂体腺瘤的治疗——尤其是在非PRL 型腺瘤的治疗中,发挥更积极的作用。

Dopamine is the predominant catecholamine neurotransmitter in the human central nervous system. It plays an important role both in the human central nervous system and the periphery nervous system. The dopamine D2 receptor expressed in the anterior and intermediate lobes of the pituitary gland, where they inhibit the secretion of prolactin （PRL） and Melanocyte-Stimulating Hormones （MSH）. The dopamine D2 receptor has been found in the majority of prolactinomas. Dopamine D2 receptor agonists are clinically effective in control grow of these tumors. It has become the primary therapeutic method for the majority of such tumors. Aceompanied by the development of techniques on molecular biology and radiological medicine, great advancements have been made in the research on D2 dopamine receptor. Besides the prolactinomas, the dopamine D2 receptors have been identified in other kinds of pituitary adenoma. The therapeutic effectiveness of D2 receptor agonists on these tumors has been evaluated. Furthermore, the expressed subtypes of dopamine D2 receptors have been identified in some pituitary adenomas, which are correlated with the therapeutic response to D2 receptor agonists. There are still some controversies over the expressions of dopamine D2 receptors and the function of dopamine agonist treatment. We anticipate that the D2 receptor agonist may play more active roles in the management of pituitary adenomas, including non-prolactin-secreting pituitary adenomas, based on the development of techniques on molecular biology and pharmacology.