Evolution of the GnRH Neuron
摘要
The 8–11 amino acid peptides gonadotropin-releasing hormone (GnRH), adipokinetic hormone (AKH) and corazonin represent a superfamily that evolved in Bilateria nearly one billion years ago. While these peptides have been employed for many different types of intercellular signaling, a relatively consistent neuroendocrine-type function is evident. In invertebrates, AKH, and corazonin neurons are found to have prominent roles in coordinating energy metabolism responses. The classical hypophysiotropic GnRH neuron appears to become evident only during chordate evolution. The tunicate Ciona intestinalis has a neurogenic olfactory placode from which GnRH neurons are born that have roles in metamorphosis and adult fertility. Two rounds of whole-genome duplication in vertebrates and subsequent species-specific loss events have resulted in the variable existence of GnRH1, GnRH2, and GnRH3 neurons. The basal forebrain GnRH1 neurons always represent the hypophysiotropic neuroendocrine population, except in some fish where GnRH1 has been lost and is replaced by GnRH3. In rodents and primates, multiple extrahypothalamic neural populations coexpress low levels of GnRH1 that very likely have unrelated functions. The midbrain GnRH2 neurons are the most highly conserved population in vertebrates but appear to have little role in fertility control. Within mammals, the functional impact of subtle species variations in hypophysiotropic GnRH1 neuron distribution and morphology remain unknown. However, the mammalian requirement for pulsatile GnRH secretion, as well as a sophisticated mechanism for controlling the preovulatory surge, has likely resulted in the adoption of kisspeptin pulse and surge generators as core elements of the GnRH neuronal network.