促肾上腺皮质激素细胞肿瘤生化静默机制研究进展

Recent advance in silencing mechanism of corticotroph tumors

促肾上腺皮质激素细胞肿瘤(CTs)根据患者有无库欣病表现可以分为功能型CTs和静默型CTs(SCTs)2种亚型。2种亚型肿瘤的病理表现一致,免疫组织化学染色检测均可见促肾上腺皮质激素(ACTH)和T-box转录因子19的表达,但SCTs患者外周血ACTH水平正常,无库欣病表现,且表现为侵袭性生长,术后复发率高。有研究表明SCTs生化静默的机制涉及阿片黑素皮质素原(POMC)(ACTH前体)基因的表达和ACTH分泌的各个过程。本文现围绕正常腺垂体细胞ACTH生理合成及调控,SCTs中POMC基因的转录、转录后调控、翻译后调控以及ACTH分泌异常等方面对SCTs的生化静默机制进行综述,以期为SCTs的研究和临床诊治提供参考。

Corticotroph tumors(CTs)are classified into functional CTs and silent CTs(SCTs)according to presence or absence of Cushing's disease manifestations.The pathological manifestations of functional CTs and SCTs are consistent,and both adrenocorticotrophic hormone(ACTH)and T-box transcription factor TBX19 expressions are seen by immunohistochemistry.SCTs have normal peripheral blood ACTH levels,without Cushing's disease manifestations;and SCTs exhibit invasive growth with high recurrence rate.Some studies have suggested that the biochemical silencing mechanism of SCTs involves pro-opiomelanocortin(POMC,ACTH precursor)gene expression and ACTH secretion.In this paper,the biochemical silencing mechanism of SCTs will be reviewed from aspects of physiological synthesis and regulation of ACTH in normal adenohypophysial cells,and transcription,post-transcriptional regulation,and post-translational regulation of POMC gene,and ACTH abnormal secretion in SCTs.