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Different neuroparsin variants were initially identified as anti-gonadotropic peptides from the pars intercerebralis-corpora cardiaca complex of the migratory locust, Locusta migratoria, and further studies revealed the pleiotropic activities of these peptides. Subsequently, additional neuroparsin-like peptides were discovered from other arthropod species. Studies in mosquitoes and locusts suggest that members of this conserved peptide family are involved in the regulation of insect reproduction and can even serve as molecular markers of the fascinating biological process of locust phase transition. Sequence analysis and multiple alignments revealed pronounced sequence similarities between arthropod neuroparsins and the N-terminal, growth factor binding region of vertebrate and mollusc insulin-like growth factor binding proteins (IGFBP). This observation led to the hypothesis that neuroparsins might interact with endogenous insulin-related peptides. The present paper gives an overview of several neuroparsin family members that have hitherto been described in insects, as well as of a number of newly identified neuroparsin precursors from other species.

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Members of the insulin superfamily are not restricted to vertebrates, but have also been identified in invertebrate species. In the current report, we present the characterization of Scg-insulin-related peptide (IRP), an insulin-related peptide in the desert locust, Schistocerca gregaria. This peptide was isolated from corpora cardiaca (CC) extracts by means of a high-performance liquid chromatography (HPLC)-based purification strategy. Subsequent cloning and sequencing of the corresponding cDNA revealed that the encoded Scg-IRP precursor displays the structural organization that is typical for members of the insulin superfamily. Moreover, immunocytochemistry on brain tissue sections demonstrated the presence of Scg-IRP in median neurosecretory cells of the pars intercerebralis and their projections towards the storage part of the CC. Quantitative real-time RT-PCR studies revealed the presence of Scg-IRP transcripts in a variety of tissues, including nervous tissue and fat body. Furthermore, these transcripts showed a tissue-and phase-dependent, temporal regulation during the reproductive cycle of adult males and females. Finally, we demonstrated that Scg-IRP interacts in vitro with a recombinant neuroparsin, a locust protein displaying sequence similarity with vertebrate IGF binding proteins.

This study describes the identification and distribution of two novel neuroparsin precursor transcripts (Scg-NPP3/Scg-NPP4) in the desert locust, Schistocerca gregaria. Unlike Scg-NPP1 and Scg-NPP2, both transcripts were not only detected in the brain, but also in various other tissues, such as fat body, ventral nerve cord, testis and male accessory glands. Northern analysis showed that the levels of these transcripts are regulated during larval development, as well as during moulting and reproductive cycles. A significant increase in both mRNAs was observed during the period that just precedes the initial sexual activity of adult females and males. In silico analysis of sequence databases revealed the existence of several other neuroparsin-like peptides in a variety of arthropod species, including crustaceans and chelicerates. Neuroparsins also display similarities with vertebrate IGFBP.

Neuroparsins were originally identified in locust corpus cardiacum extracts as folliculostatic or 'antigonadotropic' neuropeptides. This paper presents the cloning of two different neuroparsin precursor cDNAs from the brain of the desert locust, Schistocerca gregaria. The first transcript encodes the precursor (Scg-NPP1) of S. gregaria neuroparsin A and B, whereas the second codes for a novel neuroparsin-related peptide precursor (Scg-NPP2). Both precursors display significant sequence similarities with each other and with the Locusta migratoria neuroparsin (Lom-NPP) and Aedes aegypti ovary ecdysteroidogenic hormone (Aea-OEH1) precursors. Northern blot analysis revealed that these neuroparsin transcripts are present in larval and adult locust brains. Interestingly, the Scg-NPP2 mRNA content proved to be strongly regulated during the reproductive cycle in both adult males and females.

This review summarizes recent advances and novel concepts in the area of insect reproductive neuroendocrinology. The role of ÔclassicÕ hormones, such as ecdysteroids and juvenoids, to control reproduction is well documented in a large variety of insect species. In adult gonads, ecdysteroids appear to induce a cascade of transcription factors, many of which also occur during the larval molting response. Recent molecular and functional data have created opportunities to study an additional level of regulation, that of neuropeptides, growth factors and their respective receptors. As a result, many homologs of factors playing a role in vertebrate reproductive physiology have been discovered in insects. This review highlights several neuropeptides controlling the biosynthesis and release of the ÔclassicÕ insect hormones, as well as various peptides and biogenic amines that regulate behavioural aspects of the reproduction process. In addition, hormone metabolizing enzymes and second messenger pathways are discussed with respect to their role in reproductive tissues. Finally, we speculate on future prospects for insect neuroendocrinological research as a consequence of the recent ÔGenomics RevolutionÕ.In metazoans, sexual reproduction is the most widespread mechanism to generate offspring and to preserve the existing diversity of populations and species. The developmental process that leads to the production of gametes in sexually mature animals starts early in the embryo and the physiological activity of the gonads is strictly regulated by endo-, paraand autocrine factors. The huge success of insects (Hexapoda) as the most diverse and numerous group of the animal kingdom is at least partly based on their complex, but efficient, reproduction process. Until recently, the study of insect reproductive physiology mainly focused on elucidating the role of the ÔclassicÕ insect hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), also known as the Ômolting hormoneÕ. However, novel molecular and functional data on regulatory peptides and signal transducing receptors, and the availability of continuously expanding genome and Ôexpressed sequence tagsÕ sequence databases provide us with a burst of information that sheds new light on the molecular mechanisms involved in insect reproduction. The present review addresses the role of physiological regulators (i.e. hormones and paracrines) during the reproductive life stage. Role of ÔclassicÕ insect hormones

Control of gonad development in insects requires juvenile hormone, ecdysteroids, and a peptidic brain gonadotropin(s). Compared to vertebrates, the situation in insects with respect to the molecular structure of gonadotropins is far less uniform. Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) of vertebrates are glycoproteins that are synthezised in the hypothalamus and released from the anterior pituitary. They stimulate gonad development, the production of progesterone or of sex steroids (estrogens, androgens). None of the known insect gonadotropins is a glycoprotein, neither can they be grouped into a single peptide family. In Drosophila, two G-protein coupled receptors, structurally related to the mammalian glycoprotein hormone receptors, have been identified. Nothing is known about their natural ligands. The sex-steroids of insects are likely to be ecdysteroids (20E in females, E in males of some species). Some of the identified gonadotropins speed up vitellogenesis (locust OMP and some -PF/-RFamide peptides) or stimulate ecdysteroid production by the ovaries (locust-OMP and Aedes- OEH) or testis (testis ecdysiotropin of Lymantria). In flies, the only as yet identified gonadotropin is the cAMP-generating peptide of Neobellieria. The seeming absence of uniformity in gonadotropins in insects might be due to a multitude of factors that can stimulate ecdysteroid production and/or to the use of different bioassays. Arch.