After initial challenges with vehicle alone and then 10 micrograms/kg human pancreatic
tumor GH-releasing factor (hpGRF)-40, six adult subjects who had presented in childhood with idiopathic GH deficiency were given 0.33 micrograms/kg
hpGRF-40, iv, every 3 h for 5 days. Serum GH levels were monitored daily for 90 min after the 0800 h doses of 0.33 micrograms/kg
hpGRF-40, and serum
somatomedin C was measured at 0800 and 2000 h. In addition, plasma levels of
cholesterol,
high density lipoprotein cholesterol, and
triglycerides were measured daily at 0800 h. Three hours after the last 0.33 micrograms/kg dose, all subjects were rechallenged with 10 micrograms/kg
hpGRF-40. In response to the initial 10 micrograms/kg challenge with
hpGRF-40, and although serum GH levels rose in two of six subjects, the mean maximum GH level achieved was no different from that
after treatment with vehicle alone. Within 12 h after initiation of the intermittent administration of
hpGRF-40, mean +/- SEM serum
somatomedin C had risen by 0.1 +/- 0.05 U/ml, and at the end of the 5-day period, had increased from 0.24 +/- 0.07 to 0.78 +/- 0.32 U/ml. In response to the second challenge with 10 micrograms/kg
hpGRF-40, serum GH levels rose in three of the four subjects who initially failed to respond or had a less than 1 ng/ml GH response. The increase in serum GH was greater in one of the two subjects who had responded to the first dose. In addition, unlike the first dose, the mean maximal serum GH level achieved in response to the second 10 micrograms/kg dose of
hpGRF-40 was higher than that in response to vehicle (P = 0.031). Although there was no statistically significant change during the 5-day period, in plasma
cholesterol,
high density lipoprotein cholesterol, or
triglycerides, the latter exhibited a trend toward increased levels. Our preliminary data show that 5 days of intermittent
hpGRF-40 administration augment GH secretion in some adults with GH deficiency, suggesting that somatotropes are present in idiopathic GH deficiency and may be primed by
hpGRF-40. The rise in serum
somatomedin C to normal levels after multiple
injections of
hpGRF-40 is encouraging, since circulating levels of
somatomedin C may be more important than the increase in immunoreactive GH levels as an index of response for induction of linear growth. The demonstration of
biological effects of
hpGRF-40 in all six subjects without any serious adverse effects suggests that
hpGRF-40 has promise in the treatment of GH deficiency.