Invertebrate Gonadotropin-Releasing Hormone Receptor Signaling and Its Relevant Biological Actions

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.

Gonadotropin-releasing hormone-like receptor 2 inversely regulates somatic proteostasis and reproduction in Caenorhabditis elegans

“…GnRH-like signaling in invertebrates regulates various aspects of reproduction and associated reproductive treats ( Sakai et al, 2020 ). Likewise, somatic activation of the gonadal longevity pathway is coupled with reproduction ( Shemesh et al, 2017b ).…”

“…The gonadotropin-releasing hormone (GnRH) superfamily acts at the interplay between development and reproduction. This superfamily integrates internal and environmental stimuli to regulate sexual maturation and reproductive functions in vertebrates and invertebrates ( Zandawala et al, 2018 ; Sakai et al, 2020 ). This G protein-coupled receptor (GPCR) superfamily is subdivided into two main subfamilies based on neuropeptides sequence conservation.…”

From Dark to Light – An Overview of Over 70 Years of Endocrine Disruption Research on Marine Mollusks

“…At the time, this further strengthened the assumption that invertebrate and vertebrate endocrinology are similar including the presence of a homologous system for the vertebrate hypothalamic-pituitary-gonadal axis. Since then we have found that these peptides are multifunctional and do not have a specific reproductive function as seen in vertebrates (38)(39)(40)(41)(42)(43). As a result, more studies have investigated these peptides and/or their assumed related molecules [e.g., follicle-stimulating hormone (FSH)] in mollusks with antibodies raised against vertebrate molecules (44-47); most likely resulted in non-specific results and so inappropriate conclusions.…”

The Effects of Zearalenone on the Localization and Expression of Reproductive Hormones in the Ovaries of Weaned Gilts

“…Gonadotropin releasing hormone receptor (GnRHR) is a G protein coupled receptor. Previous studies have indicated that GnRH combines with GnRHR on the target cell membrane, and activates the intracellular signaling pathway to complete its biological function [ 16 , 17 ]. Follicle stimulating hormone receptor (FSHR) is an important member of HPG axis, which plays a vital role in granulosa cell (GC) proliferation, apoptosis and differentiation, as well as follicle development and ovulation [ 18 , 19 ].…”