A new member of the hypothalamic RF‐amide peptide family, LPXRF‐amide peptides: Structure, localization, and function

Abstract

Recently, we identified a novel hypothalamic neuropeptide with a C-terminal LPLRF-amide sequence in the quail brain. This avian neuropeptide was shown to inhibit gonadotropin release from the cultured anterior pituitary. This peptide is the first hypothalamic peptide that inhibited gonadotropin release reported in vertebrates. We, therefore, termed it gonadotropin-inhibitory hormone (GnIH). After this finding, we found that GnIH-related peptides were present in the brains of other vertebrates, such as mammals, amphibians, and fish. These GnIH-related peptides possessed a LPXRF-amide (X=L or Q) motif at their C-termini in all investigated animals. Mass spectrometric analyses combined with immunoaffinity chromatography were powerful techniques for the identification of mature endogenous LPXRF-amide peptides. The identified LPXRF-amide peptides were found to be localized in the hypothalamus and brainstem areas, and to regulate pituitary hormone release. Subsequently, cDNAs that encode LPXRF-amide peptides were characterized in vertebrate brains. In this review, we summarize the identification, localization, and function of a new member of the hypothalamic RF-amide peptide family, LPXRF-amide peptides in vertebrates. Recent studies on the receptors for LPXRF-amide peptides will also be reviewed.

Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat

“…Similarly to other reports (Kriegsfeld et al, 2006;Ukena and Tsutsui, 2004), RFRP-3 cell bodies and fibers were observed throughout the diencephalon and the amygdala in the male rat. Dense networks of fibers were found in the medial amygdala (mAg), the medial preoptic area (mPOA), the bed nucleus of the stria terminalis (BnST), and the periventricular thalamic nucleus of the thalamus (PVT)-areas of the brain that are known to regulate the HPG, male sex behavior and food intake (For review see (Cunningham, Clifton, and Steiner, 1999;Fabbri, Jannini, Gnessi, Ulisse, Moretti, and Isidori, 1989;I'Anson, Foster, Foxcroft, and Booth, 1991)).…”

“…Recent studies have suggested that stimulatory neuropeptide systems, such as galanin-like peptide (GALP), are critical for maintaining reproductive physiology and behavior, but a loss of GALP expression or activity is insufficient to account for the complete loss of reproductive function in diabetic rats; these observations suggests that other inhibitory factors may be involved (Stoyanovitch, Johnson, Clifton, Steiner, and Fraley, 2005a). A recently discovered RFamide peptide family has proven to contain prime candidates to fill this role as an endogenous inhibitory factor to reproduction (Kriegsfeld, Mei, Bentley, Ubuka, Mason, Inoue, Ukena, Tsutsui, and Silver, 2006;Tsutsui, Saigoh, Ukena, Teranishi, Fujisawa, Kikuchi, Ishii, and Sharp, 2000;Ukena and Tsutsui, 2004;.…”

“…The neuropeptide FMRFamide was first described in the venus clam and RFamide peptides were later found in many vertebrate species (for review of the RFamide peptides see: Ukena and Tsutsui, 2005)). Avian GnIH is an endogenous neuropeptide that elicits strong inhibitory actions on gonadotropin secretion--central administration of GnIH in birds is known to elicit a dramatic decrease in GnRH-mediated LH secretion and inhibit sex behaviors .…”

Positive selection effects on the biochemical properties of mammal pyroglutamylated RFamide peptide receptor (QRFPR)

“…In the past, the existence of five groups within the RFamide peptide family was recognized in vertebrates, namely the neuropeptide FF (NPFF) group, the prolactin-releasing peptide (PrRP) group, the gonadotropin-inhibitory hormone (GnIH) group, the kisspeptin group and the 26RFa/QRFP group (Chartrel et al 2011;Leprince et al 2013). These RFamide peptides have been shown to exert important neuroendocrine, behavioral, sensory and autonomic functions (Ukena & Tsutsui 2005;Tsutsui & Ukena 2006). Among those, NPFF is well known as a morphine modulatory peptide (Panula et al 1999).…”

Positive selection effects on the biochemical properties of fish pyroglutamylated RFamide peptide receptor (QRFPR)

“…In the past, the existence of five groups within the RFamide peptide family has been recognised in vertebrates, namely the neuropeptide FF (NPFF) group, the prolactin-releasing peptide (PrRP) group, the gonadotropin-inhibitory hormone (GnIH) group, the kisspeptin group, and the 26RFa/QRFP group (Chartrel et al 2011;Leprince et al 2013). These RFamide peptides have been shown to exert important neuroendocrine, behavioural, sensory and autonomic functions (Ukena & Tsutsui 2005;Tsutsui & Ukena 2006).…”