Impaired processing of proopiomelanocortin in corticotroph macroadenomas

被引:65
作者
Gibson, S
Ray, DW
Crosby, SR
Dornan, TL
Jennings, AM
Bevan, JS
Davis, JRE
White, A
机构
[1] UNIV MANCHESTER, DEPT MED, ENDOCRINE SCI GRP, MANCHESTER M13 9PT, LANCS, ENGLAND
[2] HOPE HOSP, DEPT MED, SALFORD M6 8HD, LANCS, ENGLAND
[3] ROYAL HALLAMSHIRE HOSP, DEPT ENDOCRINOL, DIRECTORATE MED, SHEFFIELD S10 2JF, S YORKSHIRE, ENGLAND
[4] ABERDEEN ROYAL INFIRM, DEPT ENDOCRINOL, ABERDEEN, SCOTLAND
关键词
D O I
10.1210/jc.81.2.497
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed directly using a a-site immunoradiometric assay in six patients with pituitary macroadenomas (greater than or equal to 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma. ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L; normal range, <5-40 pmol/L) and significantly higher than those in microadenoma patients (median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients (median, 5:1; range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol responses varied. After CRH administration, ACTH precursors mere unchanged, whereas cortisol increased significantly, suggesting the release of biologically active ACTH. This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome, and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas may be attributable to differences in biological potency between the ACTH precursors and ACTH.
引用
收藏
页码:497 / 502
页数:6
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