Synthetic human pancreatic growth hormone releasing factor (hpGRF1-44) was given as an i.v. bolus to healthy volunteers in 5 different dosages (3.3μg to 200μg hpGRF1-44). In addition 11 healthy subjects were infused over 2 respectively 5 hours in a dosage of 100μg hpGRF1-44/h after receiving a bolus of 50 μg hpGRF1-44. Four healthy subjects served as placebo controls. GH, PRL, TSH, and GRF were measured by specific radioimmunoassays. The results show the clearcut dose response relationship between the administered GRF dosage and the resulting GH response from 3.3 to 50μg hpGRF1-44 i.v. Higher dosages of hpGRF1-44 did not lead to a more pronounced GH response though there was a linear dose response relationship between the administered hpGRF1-44 and the GRF immunoreactivity 5 minutes after injection. Infusion of hpGRF could not sustain elevated GRF levels and a second bolus of 50μg hpGRF1-44 given at the end of the 2-respectively 5-hour infusion led to a minor increase compared to the first bolus. 100μg hpGRF1-44 was given to 14 patients with active acromegaly leading to a significant rise of the GH levels with the exception of 3 patients. Of the latter 3 two had received previous therapy, and one patient suffered from ectopic GRF hypersecretion. When GH responses to hpGRF1-44 were compared to the responses to other releasing hormones there was no correlation. After transsphenoidal surgery divergent responses of GH were seen. In one patient with low basal GH and an exaggerated rise after GRF before surgery there was no response after successful transsphenoidal operation. We conclude that there is marked heterogeneity of the GH response to hpGRF1-44 in normal subjects with a dose response relationship in the low dose range which is not apparent when higher dosages above 50 μg hpGRF1-44 are used. Long-term infusion can not sustain elevated GH levels which may be explained by antagonizing factors like somatostatin. Patients with active acromegaly who have not been treated show regularly a response to hpGRF1-44, which may disappear after transsphenoidal surgery. In addition lack of GH responsiveness to hpGRF1-44 does not exclude active acromegaly in already treated patients. If untreated patients do not have a GH response after hpGRF they may have an ectopic GRF source.
ASJC Scopus subject areas
- Clinical Neurology