Mune Tomoatsu, Murase Hiroshi, Yamakita Noriyoshi, Fukuda Tetsuya, Murayama Masanori, Miura Atsushi, Suwa Tetsuya, Hanafusa Junko, Daido Hisashi, Morita Hiroyuki, Yasuda Keigo
Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan.
J Clin Endocrinol Metab. 2002 Dec;87(12):5706-13. doi: 10.1210/jc.2002-020067.
Arginine vasopressin (AVP) stimulates cortisol secretion through its vascular type V(1a) receptor in the adrenal glands, in addition to stimulating ACTH secretion through pituitary V(3) receptor. Because hyper-response of plasma cortisol to vasopressin is documented in some patients with Cushing's syndrome due to adrenal adenoma (CS) or ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), we analyzed the expression of V(1a), V(2), V(3) receptor and AVP mRNA in human adrenal tissues by quantitative competitive RT-PCR or real-time PCRs. V(1a) receptor mRNA levels (ratio against glyceraldehyde 3-phosphate dehydrogenase) were 0.378 +/- 0.143 (mean +/- SE) in preclinical CS (n = 5) and 0.630 +/- 0.072 in AIMAH (n = 4), which were significantly higher than those (0.046 +/- 0.012; n = 9) in control adrenals, whereas those in overt CS (0.143 +/- 0.048; n = 10) or aldosterone-producing adenomas (0.069 +/- 0.018; n = 12) were similar to control adrenals. Although ectopic expression of V(2) or V(3) receptor was detected in half of AIMAH cases, the absolute levels were low. Furthermore, V(1a) receptor mRNA levels in the adjacent adrenal glands (0.190 +/- 0.039, n = 9) of aldosterone-producing adenomas were higher than those in control adrenals and in the corresponding tumor portions (0.079 +/- 0.024). In contrast, there were no significant differences in AVP mRNA levels among these groups. These results suggest that eutopic V(1a) receptor overexpression is involved in the etiology of AIMAH and a subset of adrenal adenomas causing overt or preclinical Cushing's syndrome. Our results imply a possible association of V(1a) receptor expression with adrenal hyperplasia.
精氨酸加压素（AVP）除了通过垂体V(3)受体刺激促肾上腺皮质激素（ACTH）分泌外，还通过其在肾上腺中的血管V(1a)受体刺激皮质醇分泌。由于在一些因肾上腺腺瘤（CS）或ACTH非依赖性大结节性肾上腺皮质增生（AIMAH）导致的库欣综合征患者中记录到血浆皮质醇对加压素的高反应性，我们通过定量竞争性逆转录聚合酶链反应（RT-PCR）或实时PCR分析了人肾上腺组织中V(1a)、V(2)、V(3)受体和AVP mRNA的表达。临床前CS（n = 5）中V(1a)受体mRNA水平（相对于甘油醛-3-磷酸脱氢酶的比率）为0.378±0.143（平均值±标准误），AIMAH（n = 4）中为0.630±0.072，显著高于对照肾上腺（0.046±0.012；n = 9），而显性CS（0.143±0.048；n = 10）或醛固酮瘤（0.069±0.018；n = 12）中的水平与对照肾上腺相似。虽然在一半的AIMAH病例中检测到V(2)或V(3)受体的异位表达，但绝对水平较低。此外，醛固酮瘤相邻肾上腺（0.190±0.039，n = 9）中的V(1a)受体mRNA水平高于对照肾上腺和相应肿瘤部分（0.079±0.024）。相反，这些组之间的AVP mRNA水平没有显著差异。这些结果表明，原位V(1a)受体过表达参与了AIMAH以及导致显性或临床前库欣综合征的一部分肾上腺腺瘤的病因。我们的结果暗示V(1a)受体表达与肾上腺增生可能存在关联。
