GnRH-Related Neurohormones in the Fruit Fly Drosophila melanogaster.

David Ben-Menahem

doi:10.3390/ijms22095035

Abstract

Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate’s decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides and their G-protein coupled receptors have been identified. These include the adipokinetic hormone (AKH) and corazonin (CRZ) in insects and their cognate receptors that pair to form bioactive signaling systems, which network with additional neurotransmitters/hormones (e.g., octopamine and ecdysone). Multiple studies in the past 30 years have identified many aspects of the biology of these peptides that are similar in size to GnRH and function as neurohormones. This review briefly describes the main activities of these two neurohormones and their receptors in the fruit fly Drosophila melanogaster. The similarities and differences between Drosophila AKH/CRZ and mammalian GnRH signaling systems are discussed. Of note, while GnRH has a key role in reproduction, AKH and CRZ show pleiotropic activities in the adult fly, primarily in metabolism and stress responses. From a protein evolution standpoint, the GnRH/AKH/CRZ family nicely demonstrates the developmental process of neuropeptide signaling systems emerging from a putative common ancestor and leading to divergent activities in distal phyla.

Highlights

The hypothalamic–pituitary–gonadal (HPG) axis is a key endocrine axis in the reproduction of vertebrates
luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate steroidogenesis and gametogenesis in the gonads, and feedback loops consisting of gonadal hormones are involved in the regulation of gonadotropin-releasing hormone (GnRH) and gonadotropin biosynthesis to tune their levels for successful reproduction [4,5,6]
It is well established that the GnRH receptor is primarily expressed in the pituitary, though expression in additional organs has been identified, and potential effects of GnRH have been documented outside the pituitary in physiological and disease states

Summary

Introduction

The hypothalamic–pituitary–gonadal (HPG) axis is a key endocrine axis in the reproduction of vertebrates. Primary function has diverged different kingdom (forHowever, review, seetheir example [16,17,18]) It is generally acceptedinthat the of these two families, in different probablywill share common phylamembers and vary, especially among identified invertebrate species.clades, This review focus on two in evolution [17,18,19,20,21,22,23]. The AKH mammalian GnRH system based on putative similarities of the precursor gene and CRZ signaling systems have been identified in invertebrates and were linked to the organization andGnRH the processing of the to the active peptides. Drosophila AKH is an octapeptide, which was isolated from larvae and adults was identified as the ligand for a previously identified homolog of the mammalian GnRH and was detected in higher levels in females [42], and its size is about that of receptor [44,45]. The authors suggested the changes in AKH cell excitability couples nutrient sensing (e.g., low circulating sugar levels) to the exocytosis of the neurohormone to regulate metabolism, a key function of the neurohormone in adult flies ([48,49] and see below)

The AKH Receptor

Corazonin Activities in the Fly

Summary Notes