Rapid communication R7 Journal of Endocrinology (2000) 167, R7–R10 Accepted 16 October 2000 0022-0795/00/0167-00R7 © 2000 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology.org The hexapeptide KP-102 (D-Ala-D- Β-Nal-Ala-Trp-D-Phe-Lys-NH 2 ) stimulates growth hormone release in a cichlid fish ( Oreochromis mossambicus) B S Shepherd 1,2 *, S M Eckert 3 , I S Parhar 4 , M M Vijayan 5 , I Wakabayashi 6 , T Hirano 3 , E G Grau 3 and T T Chen 1 1 Biotechnology Center, University of Connecticut, Storrs, Connecticut 06269, USA 2 T.H. Morgan School of Biological Sciences, 101 Morgan Building, University of Kentucky, Lexington, Kentucky 40506-0225, USA 3 Hawaii Institute of Marine Biology, University of Hawaii, Kaneohe, Hawaii 96744, USA 4 Department of Physiology, Nippon Medical School, Tokyo 113, Japan 5 Department of Biology, University of Waterloo, Ontario N2L 3G1, Canada 6 Department of Medicine, Nippon Medical School, Tokyo 113, Japan (*To whom correspondence should be addressed, E-mail "bsshep2@pop.uky.edu") Abstract Studies in mammals have shown that synthetic Met- enkephalin derivatives, called growth hormone-releasing peptides (GHRPs), stimulate growth hormone (GH) release. The present study was conducted to determine whether the GHRP, KP-102, specifically stimulates GH release in a teleost. Tilapia (Oreochromis mossambicus) were given a single intraperitoneal injection of KP-102 (D-Ala-D-Β-Nal-Ala-Trp- D-Phe-Lys-NH2) or bovine GHRH1-29-amide or vehicle and blood was sampled at 1, 6 and 12 h after injection. KP-102 was administered at two doses of 1 ng/g and 10 ng/g body weight, whereas GHRH (positive control) was administered at a single dose of 10 ng/g body weight. Plasma levels of tilapia GH and prolactins (tPRL177 and tPRL188) were determined by radioimmunoassay. As expected, GHRH injection significantly (P <0.001) elevated plasma GH levels (ng/ml) in tilapia at 6 h post-injection. KP-102 also significantly elevated GH levels (at the low dose) at 6 (P <0.05) and 12 (P <0.01) hours post-injection. There were no significant effects on plasma PRL(s) levels, although mean levels of both PRLs were elevated at 6 h post-injection. These results show for the first time that GHRPs stimulate GH release in teleosts and suggest that the GHRP receptor and possibly a "Ghrelin-like" ligand are also present in lower vertebrates. Journal of Endocrinology (2000) 167, R7-R10 Introduction Growth hormone (GH) and prolactin (PRL) are structurally related hormones that are secreted by the vertebrate anterior pituitary, and their secretion is principally under the control of neuroendocrine factors (e.g., growth hormone-, gonadotropin- and thyrotropin-releasing hormones and somatostatin and dopamine). In addition to these regulatory factors, synthetic Met-enkephalin derivatives (hexapeptides) have also been shown to stimulate GH, and to some extent, PRL release in mammals (Bowers et al. 1990, Elias et al. 1995, Bowers 1998). These hexapeptides, also termed growth hormone- releasing peptides (GHRPs), have been extensively studied and have been shown to safely stimulate pulsatile GH release and consequently growth in mammals and humans (Baker et al. 1984, Thorner et al. 1997, Bowers 1998, Camanni et al. 1998, Mericq et al. 1998). Studies in mammals have shown that GHRPs stimulate GH secretion and growth by binding to a novel receptor (Howard et al. 1996). Recently, a new endogenous protein termed "Ghrelin", which stimulates GH secretion by binding to the GHRP receptor, has been reported (Kojima et al. 1999). These findings argue for the presence of novel neuroendocrine pathways that control growth-regulating hormones in higher vertebrates. By contrast, in non-mammalian vertebrates, GHRP(s) administration, alone, has not been shown to be active in vivo (Bowers et al. 1984). Information on the activity of GHRPs in lower vertebrates will provide valuable insight into the common regulatory mechanisms that control vertebrate neuroendocrine physiology (Bowers 1998). Against this background, we examined whether the GHRP, KP-102, would stimulate GH and/or PRL levels in a teleost, the tilapia (Oreochromis mossambicus). In addition to GH, the tilapia pituitary secretes two forms of prolactin (tPRL177 and tPRL188), one of which contain 177 amino acid residues, and the other, 188 amino acid residues. These two prolactins, to which unique functions have been ascribed (Rubin & Specker 1992, Oshima et al. 1996, Sakamoto et al. 1997, Shepherd et al. 1997), are encoded by separate genes and share only 69% sequence identity (Specker et al. 1985, Rentier-Delrue et al. 1989, Yamaguchi et al. 1991). In this study, we report the effects of KP-102 treatment on circulating GH and PRL(s) levels in a cichlid teleost. Downloaded from Bioscientifica.com at 06/19/2022 02:30:37AM via free access