On thein Vitroandin VivoActivity of a New Synthetic Hexapeptide that Acts on the Pituitary to Specifically Release Growth Hormone*

Abstract

His-DTrp-Ala-Trp-DPhe-LysNH2, [His1,Lys6] GHRP, is a new synthetic hexapeptide which specifically elicits a dosage-related release of GH in vitro and in vivo without a concomitant release of LH, FSH, TSH, or PRL and, in limited in vivo studies, insulin or glucagon. Our results indicate that 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 iv, sc, or ip to rats. After iv 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 sc 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-14 and SRIF-28 inhibited the GH response of the hexapeptide; however, SRIF-28 was about four times more active than SRIF-14 in vitro and 7.5 times more active in vivo. When this small peptide was administered sc once or twice daily to immature rats for 9 or 25 days, the BW gain increased above the control. At the end of the weight gain studies the pituitary remained fully responsive to the peptide. Thus, [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 BW gain of a variety of normal animals by inducing GH release via a direct pituitary site of action.

The Endocrinology of Aging

“…These studies support the concept that somatopause is primarily hypothalamically driven and that pituitary somatotrops retain their capacity to synthesize and secrete high levels of GH. GH releasing peptides (GHRPs) are oligopeptides with even more powerful GH-releasing effects (58). Originally developed by design, it has recently been suggested that they mediate their GH-secretory effects through endogenous specific receptors (59).…”

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

“…Among these synthetic peptides, proved to be a potent releaser of GH, both in vitro and in vivo, in several species (Bowers et al, 1984;Casanueva and Dieguez, 1999). After the synthesis of GHRP-6, new peptydil (e.g., hexarelin) and non-peptydil (e.g., MK-0677) GH secretagogues (GHSs) with a higher bioavailability and a longer life span were produced (Ghigo et al, 1994;Patchett et al, 1995).…”

“…After the synthesis of GHRP-6, new peptydil (e.g., hexarelin) and non-peptydil (e.g., MK-0677) GH secretagogues (GHSs) with a higher bioavailability and a longer life span were produced (Ghigo et al, 1994;Patchett et al, 1995). These synthetic GHSs have a potent GH-releasing activity in humans, mice, rats (Bowers et al, 1977(Bowers et al, , 1984Casanueva and Dieguez, 1999; 1090-0233/$ -see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2005.04.025 Ghigo et al, 1994), swine, goats and cows (Hayashida et al, 2001).…”

In vivo effects of the GH-releasing heptapeptide GHRP-1 in lambs

“…Bowers et al [8] constructed a potent growth hormone releasing peptide (GHRP), the hexapeptide His-DTrp-AlaTrp-DPhe-Lys-NH 2 , which specifically elicited release of GH in vitro and in vivo.…”

“…causes release of GH [11]. GHRP also stimulates release of GH in rat, primate, chick, porcine, ovine and bovine species [8,10,19,20,31]. Furthermore the peptide is efficient if orally administered in rats, dogs and monkeys [43], and in man [14,27]; however, its effect is about 300-fold less potent than when administered i.v.…”