Abstract
Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproduction via the hypothalamus-pituitary-gonad axis (HPG axis) in vertebrates. GnRHs and their receptors (GnRHRs) are also conserved in invertebrates lacking the HPG axis, indicating that invertebrate GnRHs do not serve as “gonadotropin-releasing factors” but, rather, function as neuropeptides that directly regulate target tissues. All vertebrate and urochordate GnRHs comprise 10 amino acids, whereas amphioxus, echinoderm, and protostome GnRH-like peptides are 11- or 12-residue peptides. Intracellular calcium mobilization is the major second messenger for GnRH signaling in cephalochordates, echinoderms, and protostomes, while urochordate GnRHRs also stimulate cAMP production pathways. Moreover, the ligand-specific modulation of signal transduction via heterodimerization between GnRHR paralogs indicates species-specific evolution in Ciona intestinalis. The characterization of authentic or putative invertebrate GnRHRs in various tissues and their in vitro and in vivo activities indicate that invertebrate GnRHs are responsible for the regulation of both reproductive and nonreproductive functions. In this review, we examine our current understanding of and perspectives on the primary sequences, tissue distribution of mRNA expression, signal transduction, and biological functions of invertebrate GnRHs and their receptors.
Highlights
Reproduction is one of the most fundamental physiological functions for the continued existence and evolution of an animal
The hitherto-elucidated Gonadotropin-releasing hormones (GnRHs)-GnRHs and their receptors (GnRHRs) signaling pathways in urochordates, echinoderms, and mollusks confirm that intracellular calcium mobilization is a major second messenger
The GnRHergic phospholipase Cβ (PLC)-IP3 intracellular calcium ion pathway is conserved in invertebrates
Summary
Reproduction is one of the most fundamental physiological functions for the continued existence and evolution of an animal. Most vertebrate GnRHs comprise 10 amino acids and harbor the consensus sequence pyro-Glu1-His2-Trp3-Ser, Gly, and Pro9-Gly10-amide (Table 1). These common residues are essential for receptor binding and activation [2,7]. Over the past quarter-century, GnRH-GnRHR signaling systems have been identified by molecular and in silico cloning or transcriptome analysis in invertebrate deuterostomes and protosomes: urochordates, cephalochordates, echinoderms, crustaceans, mollusks, and annelids (Table 1). These species lack a hypothalamus and pituitary. We summarize our current understanding of the primary sequences, tissue distribution, signaling cascades, and biological functions of invertebrate GnRHs and their receptors
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