ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE

His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, [His1,Lys6]GHRP [growth hormone-releasing peptide], is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH [growth hormone] in vitro and in vivo without a concomitant release of LH [luteinizing hormone], FSH, TSH or PRL [prolactin] and, in limited in vivo studies, insulin or glucagon. This small peptide has the attributes of a hypophysiotropic hormone. In vitro the minimum and maximum active dosages ranged from 1-10 ng/ml in the pituitary incubate assay. It was active in rats, monkeys, lambs, calves and under special experimental conditions, chicks, indicating its lack of species dependency. It was active when administered i.v., s.c. or i.p. to rats. After i.v. injection, GH levels rose within 2 min, peaked at +10-20 min, and by 2 h usually had returned to normal. It was not possible to directly compare the potencies of [His1,Lys6]GHRP and the GH-releasing factors GHRF-44 and GHRF-40 after a single s.c injection in rats because the time course of the GH response of these peptides was different. The GH response of [His1,Lys6]GHRP was longer in duration than either of these larger peptides. Both SRIF[somatostatin]-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about 4 times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered s.c. once or twice daily to immature rats for 9 to 25 days, the body weight gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. [His1,Lys6]GHRP may be a valuable peptide for investigating the function of the pituitary somatotrophs and, in addition, it has the potential for increasing body weight gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.