Pituitary Actions of RFamide Peptides: A Critique of the Evidence

RFamides are a relatively recently-discovered class of peptides characterised by an arginine-phenylalanineamide at their C terminus. In mammals, all of the five known RFamide families (neuropeptide FFs, prolactin-releasing peptides, RFamide-related peptides, kisspeptins and pyroglutamylated RFs) were originally discovered as neuropeptides influencing central nervous system functions such as reproduction, feeding behavior and nociception; however presence of their G-protein-coupled receptors in the pituitary gland has led to speculation that they also influence the function of this gland by either autocrine/paracrine or neuroendocrine mechanisms. In support of such actions, prolactin-releasing peptide is produced locally within the pituitary gland, and pulses of neuropeptide FF are secreted into blood from nerve terminals in the posterior pituitary lobe originating from the hypothalamus. In contrast, it is argued that the balance of experimental evidence does not yet support such roles for RFamide-related peptides, kisspeptins and pyroglutamylated RF peptides due to their absence or scarcity in the neurosecretory zone of the median eminence, blood and pituitary tissue. In some cases, assignment of functional nomenclature has been based on inconclusive evidence of the proposed function, causing confusion in the field. To resolve these issues it will be important to compare the peptide concentrations required to elicit pituitary effects with those found in portal and peripheral blood and in pituitary tissue. To date this has only been systematically done for kisspeptin, for which the portal blood concentration was found to be several orders of magnitude lower than that which stimulated gonadotrophin release from primary pituitary cell cultures.