RFamide peptides as mediators in environmental control of GnRH neurons

Hypothalamic gonadotropin-releasing hormone (GnRH) is a key hormone for reproductive functions in vertebrates and non-vertebrates. Although GnRH neuronal system is regulated by several factors such as steroids, neurotransmitters and neuropeptides, it is not fully understood how environmental signals control the GnRH neuronal system. RFamide peptides, members of peptides possessing an Arg-Phe-NH2 motif at their C-terminus, have recently been characterized as major regulators of GnRH neurons. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH), are emerging as important regulators of the reproductive axis. Kisspeptin acts as the accelerator, directly driving GnRH neurons, whereas GnIH acts as the restraint. In addition, other RFamide peptides such as prolactin-releasing peptide (PrRP), PQRFa peptide, 26RFa/QRFP are also known to control reproduction. These RFamide peptides are regulated by environmental factors such as photoperiods, steroid hormones, metabolic signals, and stress. How environmental signals are integrated by RFamide peptides to regulate reproduction through the GnRH neurons?

► We reviewed each member of RFamide neuropeptides from the point of view of gene evolution, neuronal localization and their fiber projection, receptors, and functions.
► More emphasis was given to the information of RFamides in non-mammalian species and their functions in reproduction.
► To provide overview of the regulatory system of RFamides, we summarized the regulation of RFamide secretion by environmental factors including photoperiods, steroid hormones, metabolic signals and stress.
► Finally we provided a conceptual figure of the mediatory role of RFamides in the control of reproductive system.