The interaction of growth hormone releasing hormone and somatostatin in the generation of a GH pulse in man.
Hindmarsh PC., Brain CE., Robinson IC., Matthews DR., Brook CG.
OBJECTIVE: To study the regulation of the growth hormone (GH) response to growth hormone releasing hormone (GHRH) in the presence or absence of somatostatin pretreatment. DESIGN: Seven healthy adult male volunteers of normal height and weight and aged between 19 and 29 years underwent four separate studies (each containing three cycles in one day) in random order. The studies were separated from each other by at least a week. On day 1, three consecutive cycles (between 0800 and 2000 hours) consisted each of a saline infusion for 3 hours which was stopped prior to a bolus injection of saline and followed by 60 minutes of more intensive blood sampling. On day 2, the bolus injections were of GHRH given after saline infusion. On days 3 and 4 somatostatin infusions were administered instead of saline over the 3-hour periods followed by bolus injections of saline or GHRH respectively. In all studies, samples were collected for the measurement of serum GH concentration at 15-minute intervals from time 0 to 180 minutes and then at 5-minute intervals for a further 60 minutes, this cycle being repeated three times. MEASUREMENTS: Serum GH concentrations were analysed by serial array averaging. RESULTS: Prompt release of GH was observed in response to GHRH given against a saline background (day 2, cycle 1) (mean at 60 minutes 49.2 +/- 14.7 mU/l) but the responses observed during the second and third cycles were attenuated (mean at 60 minutes 17.2 +/- 4.0 mU/l; P = 0.025). GH release between somatostatin infusions (somatostatin withdrawal; day 3) occurred twice as often as that observed during saline infusions (62% day 3: 29% day 1). The response, although qualitatively similar to that induced by GHRH, was reduced in amplitude and the time of onset variable (5-45 minutes). On day 4, the administration of GHRH as a bolus injection combined with somatostatin withdrawal led to consistent and repeatable GH responses (mean at 60 minutes, cycle 1, 39.7 +/- 10.8 mU/l; cycles 2 and 3, 37.4 +/- 9.4 mU/l) which were similar to those observed with GHRH alone (day 2, cycle 1) (mean 39.7 +/- 10.8 mU/l) (P = NS). CONCLUSIONS: These data suggest that endogenous somatostatin secretion is important in determining the ability of the somatotroph to respond to repeated growth hormone releasing hormone stimulation and that for regular GH pulse generation a close interplay between growth hormone releasing hormone and somatostatin is required.