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.
Adams
E F
EF
Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Federal Republic of Germany.
Buchfelder
M
M
Lei
T
T
Petersen
B
B
Fahlbusch
R
R
D000172:Acromegaly / Q000235:genetics*; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008967:Molecular Biology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C039542:somatocrinin receptor; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D019205:GTP-Binding Protein alpha Subunits, Gs