Study of the role of novel RF-amide neuropeptides in affecting growth hormone secretion in a representative non-human primate (Macaca mulatta)

Abstract

RF amide peptide family with distinctive terminal -Arg-Phe-NH(2) signature is evolutionarily conserved from invertebrates to mammals. These neuropeptides have been shown to affect diverse functions in invertebrates and vertebrates including influencing pituitary hormone secretion. More recently, two members of this family 26-amino acid and 43-amino acid RF amide peptide (26RFa and 43RFa, respectively) originally isolated from frog have been cloned in rats and humans. Actions of these peptides on hormone secretion have not been studied in primates. In the present study, effect of iv administration of three different doses of human 26RFa and 43RFa on GH secretion was studied in a representative higher primate, the rhesus monkey. As control against these two peptides, normal saline and a scrambled sequence of 26RFa was administered. A set of four intact adult male monkeys received the administration in a random order. Peripheral blood samples were obtained from the chairrestrained but fully conscious animals for a period of 30 min before and 240 min after the administration at 15-min intervals. For quantitative measurement of GH concentration, a human GH chemiluminescent immunometric assay was used. Peripheral administration of 38 and 76 nmol doses of 26RFa significantly (P < 0.05) stimulated GH AUC during a 0-120 min period after injection of 26RFa. In contrast to 26RFa, administration of 43RFa appeared to suppress GH levels during the later stages of the sampling i.e. from 120 to 240 min period. Mean AUC during the period was significantly (P < 0.05) reduced by 76 nmol dose of 43RFa, while 38 nmol dose of 43RFa also had similar effect but lacked full statistical significance (P = 0.058). To our knowledge present study reports for the first time-specific stimulatory effect of 26RFa on the GH secretion and a novel inhibitory and delayed effect of 43RFa on the GH secretion in higher primates. In conclusion, present findings extend evidence for endocrine actions of RF amides in primates and suggest differential effect of these peptides on GH secretion in primates.

MOLECULAR EVOLUTION OF GPCRS: 26Rfa/GPR103

“…According to Alonzeau et al (2013), 26RFa/QRFP is also expressed in human prostate cancer and stimulates the neuroendocrine differentiation and migration of cancer cells. Administration of 26RFa/QRFP in the brain increases plasma luteinizing hormone (LH) levels in both sexes in rat (Navarro et al 2006, Patel et al 2008 and stimulates prolactin and growth hormone secretion in male rhesus monkeys (Qaiser et al 2012. Intrathecally administered 26RFa/QRFP induces analgesic effects in rat under formalin and carrageenan tests (Yamamoto et al 2008).…”

Maternal Engineered Nanomaterial Inhalation During Gestation Disrupts Vascular Kisspeptin Reactivity

“…Kisspeptin is a member of the RF-amide peptide family, which have a distinct terminal -Arg-Phe-NH 2 (Qaiser et al, 2012), are evolutionarily conserved from invertebrates to mammals and have been shown to have important physiological roles in reproduction (d'Anglemont de Tassigny and Colledge, 2010) and energy balance (Castellano et al, 2010). Kiss has been shown to have key roles in reproduction including trophoblast invasion (Kotani et al, 2001), and being a neuropeptide critical for puberty (Bilban et al, 2004) and fertility (de Roux et al, 2003).…”

The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

“…Of note, in the same species, i.v. injection of 26RFa stimulates, while QRFP inhibits, growth hormone secretion (Qaiser et al, ).…”