Research article
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Abstract
The effects of GHRP-2 (also named KP102), a new growth hormone-releasing peptide, on the release of growth hormone (GH) and growth performance were examined in swine. The single intravenous (i.v.) injection of GHRP-2 at doses of 2, 10, 30 and 100 μg/kg body weight (BW) to cross-bred castrated male swine stimulated GH release in a dose-dependent manner, with a return to the baseline by 120 min. The peak GH concentrations and GH areas under the response curves (GH AUCs) for 180 min after the injections of GHRP-2 were higher (P < 0.05) than those after the injection of saline. The GH responses to repeated i.v. injections of GHRP-2 (30 μg/kg BW) at 2-h intervals for 6 h were decreased after each injection. The chronic subcutaneous (s.c.) administration of GHRP-2 (30 μg/kg BW) once daily for 30 days consistently stimulated GH release. The GH AUCs for 300 min after the injections on d 1, 10 and 30 of treatment in GHRP-2-treated swine were higher than those in saline-treated swine. However, chronic administration of GHRP-2 caused a partial attenuation of GH response between d 1 and 10 of treatment. The chronic s.c. administration of GHRP-2 also increased average daily gain for the entire treatment period by 22.35% (P < 0.05) and feed efficiency (feed/gain) by 20.64% (P < 0.01) over the saline control values, but did not significantly affect daily feed intake. These results indicate that GHRP-2 stimulates GH release and enhancing growth performance in swine.
Keywords
GHRP-2
;
GH
;
Swine
;
Growth performance
Introduction
The growth hormone-releasing peptides (GHRPs) are a family of synthetic oligopeptides, which specifically stimulate the release of growth hormone (GH) in many species as well as in humans. The first generation of GH-releasing peptide (GHRP), GHRP-6, was derived from the pentapeptide met-enkephalin through theoretic low energy conformational calculations, computer modeling, structural modification and biologic studies [1]. GHRP-6 stimulates GH release in many species [2], [3], [4]. Based on the structure of GHRP-6, a second generation of GHRP, GHRP-1, was developed. Recently, a new generation of GHRP, GHRP-2, was synthesized and reported to be a potent GH secretagogue in vitro [5], [6], [7] and in vivo in many different species [6], [8], [9], [10], [11], [12], [13] as well as in humans [14], [15], [16] after i.v., s.c., intranasal, and even oral administration. The GH-releasing activity of GHRP-2 has been found to be two to three times more active in rats and humans than GHRP-6 and GHRP-1 [14]. At present GHRP-2 seems to be the most potent member of the family of GHRPs [12], [15]. In domestic animals, the effects of GHRP-2 on the release of GH in vivo were examined in cattle [6], [8] and goats [9], [10], [12]. However, there is no report on the effects of GHRP-2 on GH release and growth performance in swine. Therefore, the aims of the present study were 1) to evaluate the GH response to single i.v. injection of GHRP-2, 2) to monitor GH responses to repeated i.v. injections of GHRP-2, and 3) to determine the effects of chronic s.c. administration of GHRP-2 on GH release and growth performance in growing swine.
Section snippets
Animals
Twenty-two cross-bred (Landrace × Large White × Duroc) castrated male swine, 110 to 130 days of age were used in three separate experiments of this study. The swine were housed in individual pens and fed ad libitum twice a day at 0900 h and 1700 h on the commercial diet for growing swine (crude protein 16%, crude fat 2.5%, crude fiber 5% and crude ash 7%). Water was provided at all times. Two days prior to the initiation of treatment, all animals were anesthetized with an i.m. injection of
GH response to single i.v. injection of GHRP-2
After the single i.v. injection of GHRP-2, plasma GH concentrations increased in a dose-dependent manner, peaked at 15 min and returned to the baseline level between 90 and 120 min (Fig. 1). Compared to the saline control group, the injection of GHRP-2 at doses of 2, 10, 30 and 100 μg/kg BW significantly (P < 0.05) increased peak plasma GH concentrations and GH AUCs for 180 min after the injections (Table 1). Administration of 100 μg of GHRP-2/kg BW elicited a higher (P < 0.05) peak GH and GH
Discussion
The present study demonstrated that GHRP-2 stimulates GH release and enhancing growth performance in swine. To our knowledge, the present study is the first investigation to assess the in vivo potency of GHRP-2 in eliciting GH release and enhancing growth performance in swine.
The single i.v. injection of GHRP-2 over the dose range of 2, 10, 30 and 100 μg/kg BW to cross-bred castrated male swine significantly stimulated plasma GH release at all doses and in a dose-dependent manner (Table 1).
Acknowledgements
We gratefully acknowledge Dr. F. A. Parlow and National Hormone and Pituitary Program (NIDDK) for providing reagents and procedures for pGH RIA, Kaken Pharmaceutical Co. Ltd., Tokyo, Japan for providing GHRP-2, and Primate Research Institute, Kyoto University, Japan for supplying normal monkey serum.
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