Parallel Studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2and Human Pancreatic Growth Hormone-Releasing Factor-44-NH2in Rat Primary Pituitary Cell Monolayer Culture*

Abstract

His-D-Trp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH [growth hormone] both in vivo and in vitro in pituitary incubates. For the 1st time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. The ED50 for GH-RP-6 was 9 nM; the ED50 for hp-GRF-44 was 1.6 nM. Ca-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 downregulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. Apparently, GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.