EFFECTS ON GROWTH HORMONE SECRETION FOLLOWING INTRAVENOUS AND SUBCUTANEOUS INJECTIONS OF GROWTH HORMONE‐RELEASING FACTOR (hGRF‐44 NH₂): COMPARISON OF IMMUNOREACTIVE PLASMA GRF LEVELS

Abstract

The effects of subcutaneous administration of three doses of human growth hormone-releasing factor (hGRF-44 NH2 or hGRF) at doses of 100, 300 and 600 micrograms were studied in six normal young men. GH responses obtained with 100 and 300 micrograms were negligible. In contrast, the 600 micrograms dose gave a profile of response comparable in timing and magnitude to that obtained with i.v. hGRF at maximal effect doses (20, 80, 100 micrograms). Plasma immunoreactive hGRF levels (IR-hGRF) were compared after s.c. and i.v. hGRF. Mean maximal plasma concentrations were comparable with s.c. 600 micrograms and i.v. 20 micrograms. Peaks occurred earlier with i.v. hGRF (5 min as opposed to 15 min): however, return to undetectable values was obtained between 90 and 120 min after s.c. or i.v. injections. These data suggest a great loss of the peptide between the subcutaneous space and blood, without delayed absorption. High variability in plasma IR-hGRF concentrations between the subjects after the same s.c. doses was observed.

Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus.

“…Thus, alternative explanations, relating to changes in the intracellular response to GRH or to changes in somatostatin secretion, appear more plausible. Other published data relating to plasma GRH levels after injection of exogenous GRH (32)(33)(34) are also likely to be incorrect, since the contribution of GRH metabolites to total measured GRH immunoreactivity is unknown. Finally, our results should be helpful in designing modifications of the GRH sequence that are resistant to enzymatic degradation in order to develop superactive analogs.…”

Characteristics of growth hormone response to the administration of growth hormone-releasing hormone (GRF) in the lamb

“…In lambs, it never lasts longer than 1 hour, whatever the dose or the route of administration, while in men it may last 2 or 3 hours (Sassolas et al, 1985). In addition, we do not observe the rebound described in bovines (Moseley et al, 1984.…”

“…However, our use of more frequent blood sampling periods has allowed us to observe multiphasic episodic secretory peaks. Using the same technique, Laurentie et al (1987) (Sassolas et al, 1985 ;Evans et al, 1985). When injected intravenously, the doses of GRF required to stimulate GH release are 10 to 100 times lower than subcutaneously.…”

Treatment with growth hormone‐releasing hormone (GHRH) 1–44 in children with idiopathic growth hormone deficiency: a randomized double‐blind dose‐effect study

“…No GH secretion was induced by placebo injections in short-term studies of subcutaneous GHRH in normal adults (Evans et al. 1985;Sassolas et al, 1985). or in children with GH deficiency (Ross et al, 1988).…”