Pivonello Rosario, Matrone Carmela, Filippella Mariagiovanna, Cavallo Luigi M, Di Somma Carolina, Cappabianca Paolo, Colao Annamaria, Annunziato Lucio, Lombardi Gaetano
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy.
J Clin Endocrinol Metab. 2004 Apr;89(4):1674-83. doi: 10.1210/jc.2003-030859.
The aim of this study was to correlate dopamine receptors and D(2) isoform expression with the cabergoline effect on alpha-subunit secretion in vitro and tumor mass in vivo in clinically nonfunctioning pituitary tumors. Eighteen patients were subjected to neurosurgery, and a tumor sample was used for dopamine receptor and D(2) isoform expression evaluation by RT-PCR and the in vitro functional studies. After neurosurgery, nine of 18 patients with persistent tumor were treated with cabergoline and tumor mass was evaluated before and after 1 yr treatment. D(2) receptor was expressed in 67% of cases. D(2long) was found in 50%, D(2short) in 17%, and both D(2) isoforms in 33% of cases. D(4) receptor was also expressed in 17% of cases. The in vitro inhibition of alpha-subunit concentration was found in 56% of cases and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). After 1 yr of cabergoline treatment, tumor shrinkage was evident in 56% of patients and was associated with D(2) expression (chi(2) = 5.6; P < 0.05). The expression of D(2short) rather than D(2long) isoform is associated with the most favorable response of the tumor to cabergoline treatment. In conclusion, this study demonstrates D(2) receptor expression and function in nearly 70% of cases, suggesting a role of this drug in the treatment schedule of clinically nonfunctioning pituitary tumors.
本研究的目的是在临床无功能垂体瘤中,将多巴胺受体及D(2)亚型表达与卡麦角林对体外α亚基分泌及体内肿瘤体积的影响相关联。18例患者接受了神经外科手术,取肿瘤样本通过逆转录聚合酶链反应(RT-PCR)评估多巴胺受体及D(2)亚型表达,并进行体外功能研究。神经外科手术后,18例有持续性肿瘤的患者中有9例接受了卡麦角林治疗,并在治疗1年前后评估肿瘤体积。67%的病例表达D(2)受体。50%的病例发现有D(2long),17%有D(2short),33%的病例同时有两种D(2)亚型。17%的病例也表达D(4)受体。56%的病例体外α亚基浓度受到抑制,且与D(2)表达相关(χ² = 5.6;P < 0.05)。卡麦角林治疗1年后,56%的患者肿瘤明显缩小,且与D(2)表达相关(χ² = 5.6;P < 0.05)。与D(2long)亚型相比,D(2short)亚型的表达与肿瘤对卡麦角林治疗的最有利反应相关。总之,本研究表明近70%的病例中有D(2)受体表达及功能,提示该药物在临床无功能垂体瘤的治疗方案中具有一定作用。