Clinical studies with human growth hormone releasing factor in normal adults and patients.
The recent availability of human growth hormone releasing factor (hGRF) encouraged thorough investigations of human growth hormone secretion. Moreover it is now possible to put forward a therapeutic application for this hormone. Herein, we report the dose-effect relationship obtained between hGRF and GH response in normal young men submitted to IV administration of doses ranging from 2.5 to 600 micrograms per subject, in three protocols. In some subjects the 2.5 micrograms dose elicited GH secretion as compared with placebo. A highly significant dose-effect was observed (based on GH-AUC and GH-peak) for doses ranging from 5 to 80 micrograms. Responses were identical above 80 micrograms. We conclude that the optimal dose required to elicit maximum GH release with minimal unwanted effects is 80 micrograms in adults. These are related to the dose and observed for doses up to 80-150 micrograms. Subcutaneous administration also induced GH-release, with relationship to the doses used (100, 300 and 600 micrograms per subject). The mean response to the highest dose (600 micrograms) was comparable in timing and magnitude to that obtained with a 100 microgram intravenous dose. Bioactivity of GH released under hGRF was proven in the Nb2 lymphoma cell multiplication assay and a high correlation was obtained between bioassay and radioimmunoassay. GH was present in blood after hGRF under 3 molecular forms corresponding to little, big and big-big GH with percentages of 50, 30 and 20, respectively. An early and slight increase in prolactin was found to be related to the hGRF doses above 80 micrograms. No change was observed for doses less than 80 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)
D000172:Acromegaly / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D001682:Biological Availability; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D013006:Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007028:Hypothalamic Hormones / Q000008:administration & dosage; D007700:Kinetics; D008297:Male; D011388:Prolactin / Q000378:metabolism
D007028:Hypothalamic Hormones; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone