White A, Clark A J
Department of Medicine, University of Manchester, Hope Hospital, Salford, UK.
Clin Endocrinol (Oxf). 1993 Aug;39(2):131-41. doi: 10.1111/j.1365-2265.1993.tb01765.x.
In recent years the techniques of molecular and cellular biology have made it possible to begin to dissect the origins and behaviour of the ACTH-secreting tumour cell. It is becoming apparent that these tumours represent undifferentiated neuroendocrine cells, and it may be that their peptide-secreting properties may have no more sinister oncological significance. However, an autocrine role for beta-endorphin may confer a selective growth advantage on the POMC-expressing cell. It is still not clear why glucocorticoids fail to inhibit the POMC gene in these extra-pituitary tumours despite the presence of glucocorticoid receptors. This may not be resolved until the mechanism for inhibition of POMC by glucocorticoids in the normal pituitary is understood, although it is tempting to speculate that a mutation in the glucocorticoid receptor or a tissue specific interaction is responsible for the resistance of POMC observed in the ectopic ACTH syndrome. In studying the peptides secreted by the extra-pituitary tumours responsible for the ectopic ACTH syndrome it would appear that direct measurement of ACTH precursors and comparison with the circulating concentrations of ACTH can give valuable information on the percentage of tumours which do not effectively process the ACTH precursors. However, far more data have to be collected on patients with occult tumours in order to identify whether this type of processing is tissue specific. Nevertheless, these studies provide useful insights into the mechanisms of intracellular signalling and regulation in such tumours which may identify unique pharmacological tools to inhibit ACTH secretion or more importantly tumour growth.
近年来，分子生物学和细胞生物学技术使人们能够开始剖析促肾上腺皮质激素（ACTH）分泌肿瘤细胞的起源和行为。越来越明显的是，这些肿瘤代表未分化的神经内分泌细胞，而且它们的肽分泌特性可能并没有更险恶的肿瘤学意义。然而，β-内啡肽的自分泌作用可能赋予表达阿黑皮素原（POMC）的细胞选择性生长优势。目前仍不清楚为什么尽管存在糖皮质激素受体，糖皮质激素却无法抑制这些垂体外肿瘤中的POMC基因。在了解正常垂体中糖皮质激素抑制POMC的机制之前，这个问题可能无法解决，尽管有人推测糖皮质激素受体的突变或组织特异性相互作用是异位ACTH综合征中观察到的POMC抵抗的原因。在研究导致异位ACTH综合征的垂体外肿瘤分泌的肽时，直接测量ACTH前体并与循环中的ACTH浓度进行比较，似乎可以提供有关未有效处理ACTH前体的肿瘤百分比的有价值信息。然而，为了确定这种处理类型是否具有组织特异性，还需要收集更多关于隐匿性肿瘤患者的数据。尽管如此，这些研究为这类肿瘤中的细胞内信号传导和调节机制提供了有用的见解，这可能有助于确定抑制ACTH分泌或更重要的是抑制肿瘤生长的独特药理学工具。
