[Gonadotrophin-releasing hormone (GnRH) in the animal kingdom]

As a major actor of the brain-pituitary-gonad axis, GnRH has received considerable attention, mainly in vertebrates. Biochemical, molecular, neuroanatomical, pharmacological and physiological studies have mainly focused on the role of GnRH as a gonadotrophin-releasing factor and have led to a detailed knowledge of the hypophysiotrophic GnRH system, primarily in mammals, but also in fish. It is now admitted that the corresponding neurons develop from the olfactory epithelium and migrate into the forebrain during embryogenesis to establish connections with the median eminence in tetrapods or the pituitary in teleost fish. However, all vertebrates possess a second GnRH system, expressing a variant known as chicken GnRH-II in neurons of the synencephalon, whose functions are still under debate. In addition, many fish species express a third form, salmon GnRH, whose expression is restricted to neurons of the olfactory systems and the ventral telencephalon, with extensive projections in the brain and a minor contribution to the pituitary. In vertebrates, GnRHs are also expressed in the gonads where they act on cell proliferation and steroidogenesis in males, and apoptosis of granulosa cells and reinititaion of meiosis in females. These functions could possibly represent the primitive roles of GnRH-like peptides, as an increasing number of studies in invertebrate classes point to a more or less direct connection between GnRH-producing sensory neurons and the gonads. According to recent studies, GnRHs appear as very ancient peptides that emerged at least in the cnidarians, the first animals with a nervous system. GnRH-like peptides have been partially characterized in several classes of invertebrates notably in molluscs, echinoderms and prochordates in which effects on the reproductive functions, notably gamete release and steroidogeneis, have been evidenced. It is possible that, with the increasing complexity of metozoa, GnRH neurons have lost their direct connection with the gonad to specialize in the control of additional regulatory centers such as the hypophysis in vertebrates or the optic gland in cephalopods. However, reminiscent effects of GnRH functions at the gonadal level would have persisted due to local production of GnRHs in the gonad itself. Altogether, these data indicate that GnRHs were involved in the control of reproduction long before the appearance of pituitary gonadotrophs.