Molecular biology of growth-hormone-secreting human pituitary tumours: biochemical consequences and potential clinical significance.

Molecular biological studies have revealed that 30-40% of GH-secreting human pituitary tumours, associated with acromegaly, harbour single-base missense mutations within the Gs alpha gene, termed gsp oncogenes. In addition, a large proportion of GH-secreting tumours inappropriately express the GH-releasing factor (GRF) gene. Gsp-oncogenes result in elevated adenylyl cyclase activity with consequent abnormally high cAMP production. In culture, GH-secreting tumours expressing gsp oncogenes respond more efficiently to the somatostatin analogue, octreotide (SMS), raising the possibility that acromegalics harbouring gsp-positive tumours may be those who optimally benefit from SMS therapy. Inappropriate expression of GRF may result in abnormal presence of a positive autocrine feedback loop, in which secreted GRF acts on the same cells to promote cellular proliferation and GH secretion. Blockade of GRF mRNA translation by means of anti-sense oligonucleotide approaches may prove to be of value in inhibiting tumour function.