Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan, Republic of China.
Clin Endocrinol (Oxf). 2012 Feb;76(2):253-63. doi: 10.1111/j.1365-2265.2011.04179.x.
Most patients with Cushing's disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response.
A prospective study of 29 patients with CD.
Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry.
Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients.
We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.
大多数库欣病（CD）患者对促肾上腺皮质激素释放激素（CRH）或去氨加压素（desmopressin）有反应，表现为促肾上腺皮质激素（ACTH）和皮质醇水平升高。尽管位于正常促肾上腺皮质细胞上的血管加压素受体亚型是 V3 受体（V3R），但去氨加压素是一种选择性 V2 受体（V2R）激动剂，尚不清楚促肾上腺皮质细胞瘤是否表现出异常的 V2R 表达。此外，尚无研究确定 CD 患者对去氨加压素的体内反应与血管加压素受体表达之间的关系，也没有研究确定对 CRH 的反应与 CRH 受体（CRHR）表达之间的关系。因此，本研究旨在研究血管加压素受体（V1R、V2R 和 V3R）和 CRHR 在促肾上腺皮质细胞瘤上的表达及其与体内反应的可能关系。
29 例 CD 患者的前瞻性研究。
患者在手术前进行去氨加压素和 CRH 刺激试验。通过免疫细胞化学法测定促肾上腺皮质细胞瘤上血管加压素受体和 CRHR 的表达。
大多数促肾上腺皮质细胞瘤表达丰富的 V1R、V3R 和 CRHR，而 V2R 的表达差异很大，且在大腺瘤中低于微腺瘤。去氨加压素刺激试验中 ACTH 的百分比增加和 ACTH 的净 AUC 均与肿瘤体积相关。在调整肿瘤体积后，发现 ACTH 的百分比增加与 V2R 表达程度呈正相关，但与 V1R 或 V3R 无关。在 CD 患者中，肿瘤组织上 CRHR 的表达水平与 CRH 刺激后 ACTH 的百分比增加或净 AUC 之间没有关系。
我们得出结论，V2R 表达于促肾上腺皮质细胞瘤上，其表达水平与 CD 患者去氨加压素刺激后的 ACTH 反应密切相关，尽管几乎所有促肾上腺皮质细胞瘤均有丰富的 V1R 和 V3R 表达。需要进一步的研究来阐明这些受体在 CD 发病机制中的作用。
