Gonadotropin-inhibitory hormone as a regulator of social interactions in vertebrates.

The social environment changes circulating hormone levels and expression of social behavior in animals. Social information is perceived by sensory systems, leading to cellular and molecular changes through neural processes. Peripheral reproductive hormone levels are regulated by activity in the hypothalamic-pituitary-gonadal (HPG) axis. Until the end of the last century, the neurochemical systems that convey social information to the HPG axis were not well understood. Gonadotropin-inhibitory hormone (GnIH) was the first hypothalamic neuropeptide shown to inhibit gonadotropin release, in 2000. GnIH is now regarded as a negative upstream regulator of the HPG axis, and it is becoming increasingly evident that it responds to social cues. In addition to controlling reproductive physiology, GnIH seems to modulate the reproductive behavior of animals. Here, we review studies investigating how GnIH neurons respond to social information and describe the mechanisms through which GnIH regulates social behavior.

Hypothalamic inhibition of socio-sexual behaviour by increasing neuroestrogen synthesis.

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion and socio-sexual behaviours. Oestrogen (neuroestrogen) synthesized in the brain from androgen by aromatase regulates male socio-sexual behaviours. Here we show that GnIH directly activates aromatase and increases neuroestrogen synthesis in the preoptic area (POA) and inhibits socio-sexual behaviours of male quail. Aromatase activity and neuroestrogen concentration in the POA are low in the morning when the birds are active, but neuroestrogen synthesis gradually increases until the evening when the birds become inactive. Centrally administered GnIH in the morning increases neuroestrogen synthesis in the POA and decreases socio-sexual behaviours. Centrally administered 17ß-oestradiol at higher doses also inhibits socio-sexual behaviours in the morning. These results suggest that GnIH inhibits male socio-sexual behaviours by increasing neuroestrogen synthesis beyond its optimum concentration for the expression of socio-sexual behaviours. This is the first demonstration of any hypothalamic neuropeptide that directly regulates neuroestrogen synthesis.

Identification, localization and function of a novel neuropeptide, 26RFa, and its cognate receptor, GPR103, in the avian hypothalamus.

Several neuropeptides possessing the RFamide motif at their C-termini (designated RFamide peptides) have been characterized in the hypothalamus of a variety of vertebrates. Since the discovery of the 26-amino acid RFamide peptide (termed 26RFa) from the frog brain, 26RFa has been shown to exert orexigenic activity in mammals and to be a ligand of the previously identified orphan G protein-coupled receptor GPR103. Recently, we have identified 26RFa in the avian brain by molecular cloning of the cDNA encoding the 26RFa precursor and mass spectrometry analysis of the mature peptide. 26RFa-producing neurons are exclusively located in the hypothalamus whereas GPR103 is widely distributed in the avian brain. Furthermore, avian 26RFa stimulates feeding behavior in broiler chicks. This review summarizes the advances in the identification, localization, and functions of 26RFa and its cognate receptor GPR103 in vertebrates and highlights recent progress made in birds.

Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G protein-coupled receptor-103.

Several neuropeptides with the C-terminal RFamide sequence have been identified in the hypothalamus of a variety of vertebrates. Among the RFamide peptide groups, however, only LPXRFamide peptides, including gonadotropin-inhibitory hormone, have been characterized in the avian brain. In the present study, we sought for the presence of other RFamide peptides in the avian hypothalamus. We identified a cDNA encoding an RFamide peptide orthologous to 26RFa (also referred to as QRFP) in the hypothalamus of the Japanese quail. The deduced quail 26RFa precursor consisted of 120-amino-acid residues, encoding one RFamide peptide with 27 amino acids. This RFamide peptide was flanked at the N terminus by a dibasic amino acid cleavage site and at the C terminus by a glycine amidation signal. Quantitative RT-PCR analysis demonstrated specific expression of quail 26RFa mRNA in the diencephalon including the hypothalamus. Furthermore, mass spectrometry analysis revealed the presence of a peptide exhibiting the mass of mature 26RFa, indicating that the peptide is actually produced from the precursor in the diencephalon. 26RFa-producing cell bodies were localized in the anterior hypothalamic nucleus in the brain. Synthetic 26RFa increased intracellular Ca(2+) concentration in HEK293T cells transfected with the chicken G protein-coupled receptor GPR103. Intracerebroventricular injection of 26RFa in broiler chicks stimulated feeding behavior. These data provide the first evidence for the occurrence of the peptide 26RFa in the avian hypothalamus and indicate that this peptide exerts orexigenic activity.