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.
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