Peptide hormone evolution: functional heterogeneity within GnRH and CRF families

Abstract

Recent investigations indicate that the gonadotropin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF) family of peptides are each composed of at least two functionally discrete paralogous lineages. [His5Trp7Tyr8]GnRH (chicken GnRH-II) is associated with brain neuromodulatory and possibly peripheral endocrine activity, whereas [Arg8]GnRH (mammal GnRH) and its orthologues play major roles as hypothalamic releasing factors. Similarly, CRF appears to be the primary vertebrate ACTH-releasing peptide, whereas the paralogous lineage of urotensin-I-sauvagine has been associated with a variety of diverse peripheral activities. In phylogenetically older species, representatives of both GnRH and CRF family lineages have been characterized. Structural and functional conservation of these peptide systems in vertebrates suggest that additional GnRH-like and CRF-like peptides will be found in the mammal brain.Key words: neuropeptides, evolution, reproduction, HPA axis, stress, receptor–ligand interactions.