Ectopic hormone syndromes.
Ectopic hormone production is not always associated with endocrine manifestations and if extensive studies of tumour hormones are made it is found that asymptomatic hormone production is often concomitant with neoplasms. The nature of tumour hormones seems essentially indistinguishable from that of native hormones, although there exists in some cases an abundance of precursor or hormone fragments and unbalanced biosynthesis of subunits. Production of multiple hormones by a tumour is not uncommon. These facts may suggest abnormal gene expression as the basic mechanism responsible for ectopic hormone production. During the process of cellular differentiation, most of the genes are inactivated. Neoplastic transformation may activate repressed genes, thus producing hormones that are not produced by differentiated cells (derepression hypothesis). This hypothesis, however, makes it difficult to explain the higher incidence of ACTH-LPH-producing tumours among APUD tumours. Some investigators have postulated that only APUD tumours elaborate ACTH-LPH or other APUD hormones (neuro-endocrine cell hypothesis). However, there have been reported some definite non-APUD tumours which elaborate ACTH-LPH. These facts can be explained by the stepwise, irreversible repression hypothesis of cellular differentiation. In APUD cells, the gene for ACTH-LPH coding may be repressed at the terminal stage of differentiation and may, therefore, be very easily derepressed by neoplastic transformation. On the other hand, the ACTH-LPH gene may be repressed at a relatively early stage in non-APUD cells and be difficult to reactivate even after neoplastic transformation. Further studies on ectopic hormone producing tumours may clarify the mechanism of ectopic hormone production and yield new insights into the fundamental process of malignant change.