[Growth hormone receptor antagonists: potential indications].
Pegvisomant is a mutated human growth hormone molecule, which binds to the growth hormone receptor. This binding, however, does not lead to signal transduction. Therefore, in high concentrations pegvisomant acts as a growth hormone receptor antagonist. In a short term study (3 months) pegvisomant was shown to be an effective treatment for acromegaly. On theoretical grounds decreasing the biological effects of growth hormone in patients with diabetes mellitus could have a favourable impact on the severity of the secondary complications associated with this disease. Animal models for diabetic retino- and nephropathy are in accordance with this concept. Human data are lacking but clinical studies investigating the effect of pegvisomant in diabetes mellitus are in preparation. Growth hormone, either directly or via its downstream effector insulin-like growth factor-I (IGF-I) has been implicated as an important factor in the growth of malignant tumours. Animal studies in which human colon and breast cancer models were used showed that pegvisomant can powerfully decrease tumour growth. Studies in cancer patients have not yet started.
Muller
A F
AF
Erasmus Universitair Medisch Centrum, afd. Inwendige Geneeskunde, Dr. Molewaterplein 40, 3015 GD Rotterdam. muller@inw3.azr.nl
Janssen
J A
JA
de Herder
W W
WW
van der Lely
A J
AJ
D000172:Acromegaly / Q000188:drug therapy*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*
D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C406545:pegvisomant