Recent Advances in the Molecular Biology of Growth-Hormone Secreting Human Pituitary Tumours

Summary

The application of DNA technology has led to significant progress in our understanding of the aetiology of GH-secreting pituitary tumours. X-chromosome inactivation and RFLP analysis has revealed that GH-secreting tumours are monoclonal in origin and thus arise as a consequence of a somatic mutation within a single cell. Using PCR and sequence analysis, such a mutation has been identified in 30–40% of tumours. This is the socalled gsp mutation in which the gene for the α_s subunit of the G_s protein is converted to an oncogene the expression of which results in constitutive adenyl cyclase activity and thus excessive cAMP production.

In our own studies, we demonstrate that it is unlikely that a defect within the promoter region of the GH gene will prove to be a cause of excessive GH secretion in acromegaly. In contrast, we have shown that the GH gene is hypomethylated in tumour derived DNA and this may account, at least in part, for abnormal GH gene expression.

Key words

GH-secreting tumors - GH-gene promotor - GSP oncogene