No abstract

The present study investigated the GH secretory activities of two distinctively different peptides: human pancreatic GH-releasing factor 44 (GRF-44) and a synthetic peptide His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP). GH secretion was studied in perifused dispersed anterior pituitary cells from male rats 24 or 48 h postdispersion. GRF-44 was 60 times more potent than GHRP and elicited linear increases in GH secretion between 0.3 and 30 ng (0.06-6 pmol), whereas the GHRP dose range was 3-300 ng (3.44-344 pmol). Hourly pulses of GHRP (30 ng) and GRF-44 (12.5 ng) stimulated consistent GH responses. An apparent priming effect was observed with GRF-44 at a dose of 3 ng. Continuous infusion of either peptide resulted in desensitization, with GH secretion being monophasic during GHRP infusion and biphasic during GRF-44 infusion. These results demonstrate that GRF-44 and GHRP, two peptides that have striking differences in their structure and size, stimulate in vitro GH secretion with remarkable similarity. However, the differences in potency, slope of the dose response, and pattern of GH secretion during continuous GRF-44 or GHRP infusion suggest that each stimulates in vitro GH secretion by slightly different mechanisms. GHRP or similar synthetic peptides may be useful probes to study GH secretory mechanisms.

The characterization of GH-releasing peptides in vivo has been complicated by the effects of endogenous hypothalamic regulation of GH secretion. We describe a model to minimize endogenous hypothalamic interference by pretreating adult male rats with iv diethyldithiocarbamate and antisomatostatin serum. This pretreatment regimen established stable, detectable basal levels of plasma GH and eliminated spontaneous GH pulses for 12 h. Repeated pulsatile administration of 400 ng/kg iv rat hypothalamic GH-releasing factor (rGRF) produced consistent GH responses. Linear, nearly identical, dose responses (from 300-5000 ng/kg) were observed with rGRF and human pancreatic GH-releasing factor (GRF44) with ED50 values of 1059.3 and 1116.9 ng/kg, respectively. We also investigated a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP), which was previously reported to have potent GH-releasing activity. In contrast to either rGRF or GRF44, repeated administration of the same dose of GHRP did not produce consistent GH responses. The first bolus of GHRP produced a larger GH pulse than the second (P less than 0.01), followed by increasing GH responses from injections 2 to 7. GHRP was about 2 log orders less potent than either rGRF or GRF44 on a molar basis. The disparity between the native peptides and GHRP suggests that the synthetic peptide may act to release GH through a different mechanism(s). In summary, these data indicate that the diethyldithiocarbamate/anti-somatostatin serum-treated animal may be a useful model for investigating the pituitary actions of GH-releasing peptides.