Metamorphosis endowed the insects with properties that enabled them to conquer the Earth. It is a hormonally controlled morphogenetic process that transforms the larva into the adult. Metamorphosis appeared with the origin of wings and flight. The sesquiterpenoid juvenile hormone (JH) suppresses wing morphogenesis and ensures that metamorphosis takes place at the right ontogenetic time. This review explores the origin of insect metamorphosis and the ancestral function of JH. Fossil record shows that the first Paleozoic winged insects had (hemimetabolous) metamorphosis, and their larvae were likely aquatic. In the primitive wingless silverfish that lacks metamorphosis, JH is essential for late embryogenesis and reproduction. JH production after the embryo dorsal closure promotes hatching and terminal tissue maturation.

• MeSH
• biologická evoluce * MeSH
• biologická proměna MeSH
• hmyz * růst a vývoj   fyziologie   MeSH
• juvenilní hormony MeSH
• larva růst a vývoj   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• juvenilní hormony MeSH

Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the fly Drosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes. Whilst GCE/MET and AHR are phylogenetically heterologous, their mode of action is similar. JHR is targeted by several synthetic agonists that serve as insecticides disrupting the insect endocrine system. AHR is an important regulator of human endocrine homeostasis, and it responds to environmental pollutants and endocrine disruptors. Whether AHR signaling is affected by compounds that can activate JHR has not been reported. To address this question, we screened a chemical library of 50,000 compounds to identify 93 novel JHR agonists in a reporter system based on Drosophila cells. Of these compounds, 26% modulated AHR signaling in an analogous reporter assay in a human cell line, indicating a significant overlap in the agonist repertoires of the two receptors. To explore the structural features of agonist-dependent activation of JHR and AHR, we compared the ligand-binding cavities and their interactions with selective and common ligands of AHR and GCE. Molecular dynamics modeling revealed ligand-specific as well as conserved side chains within the respective cavities. Significance of predicted interactions was supported through site-directed mutagenesis. The results have indicated that synthetic insect juvenile hormone agonists might interfere with AHR signaling in human cells.

• Klíčová slova
• aryl hydrocarbon receptor, endocrine disruptors, high-throughput screening, juvenile hormone receptor, ligand binding domain,
• MeSH
• buněčné linie MeSH
• Drosophila melanogaster * metabolismus   genetika   účinky léků   MeSH
• juvenilní hormony metabolismus   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• proteiny Drosophily * metabolismus   genetika   chemie   MeSH
• receptory aromatických uhlovodíků * agonisté   metabolismus   genetika   MeSH
• signální transdukce účinky léků   MeSH
• transkripční faktory bHLH * metabolismus   genetika   agonisté   MeSH
• transkripční faktory metabolismus   genetika   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AHR protein, human MeSH Prohlížeč
• gce protein, Drosophila MeSH Prohlížeč
• juvenilní hormony MeSH
• ligandy MeSH
• MET protein, Drosophila MeSH Prohlížeč
• proteiny Drosophily * MeSH
• receptory aromatických uhlovodíků * MeSH
• transkripční faktory bHLH * MeSH
• transkripční faktory MeSH

Dietary restriction (DR) slows aging in many animals, while in some cases, the sensory signals from diet alone are sufficient to retard or accelerate lifespan. The digestive tract is a candidate location to sense nutrients, where neuropeptides secreted by enteroendocrine cells (EEC) produce systemic signals in response to food. Here, we measure how Drosophila neuropeptide F (NPF) is secreted into adult circulation by EEC and find that specific EEC differentially respond to dietary sugar and yeast. Female lifespan is increased when gut NPF is genetically depleted, and this manipulation is sufficient to blunt the longevity benefit conferred by DR. Depletion of NPF receptors at insulin-producing neurons of the brain also increases female lifespan, consistent with observations where loss of gut NPF decreases neuronal insulin secretion. The longevity conferred by repressing gut NPF and brain NPF receptors is reversed by treating adults with a juvenile hormone (JH) analog. JH is produced by the adult corpora allata, and inhibition of the insulin receptor at this tissue decreases JH titer and extends lifespan in both males and females, while this longevity is restored to wild type by treating adults with a JH analog. Overall, EEC of the gut modulate Drosophila aging through interorgan communication mediated by a gut-brain-corpora allata axis, and insulin produced in the brain impacts lifespan through its control of JH titer. These data suggest that we consider how human incretins and their analogs, which are used to treat obesity and diabetes, may impact aging.

• Klíčová slova
• aging, incretin, insulin, interorgan communication, juvenile hormone,
• MeSH
• dlouhověkost fyziologie   MeSH
• Drosophila melanogaster metabolismus   MeSH
• enteroendokrinní buňky metabolismus   MeSH
• inzulin * metabolismus   MeSH
• juvenilní hormony * metabolismus   MeSH
• mozek metabolismus   MeSH
• neurony metabolismus   MeSH
• neuropeptidy * metabolismus   MeSH
• osa mozek-střevo * fyziologie   MeSH
• proteiny Drosophily * metabolismus   genetika   MeSH
• stárnutí metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin * MeSH
• juvenilní hormony * MeSH
• neuropeptide F, Drosophila MeSH Prohlížeč
• neuropeptidy * MeSH
• proteiny Drosophily * MeSH

Juvenile hormone (JH) signaling is realized at the gene regulatory level by receptors of the bHLH-PAS transcription factor family. The sesquiterpenoid hormones and their synthetic mimics are agonist ligands of a unique JH receptor (JHR) protein, methoprene-tolerant (MET). Upon binding an agonist to its PAS-B cavity, MET dissociates from a cytoplasmic chaperone complex including HSP83 and concomitantly switches to a bHLH-PAS partner taiman, forming a nuclear, transcriptionally active JHR heterodimer. This course of events resembles the vertebrate aryl hydrocarbon receptor (AHR), activated by a plethora of endogenous and synthetic compounds. Like in AHR, the pliable PAS-B cavity of MET adjusts to diverse ligands and binds them through similar mechanisms. Despite recent progress, we only begin to discern agonist-induced conformational shifts within the PAS-B domain, with the ultimate goal of understanding how these localized changes stimulate the assembly of the active JHR complex and, thus, fully grasp the mechanism of JHR signaling.

• MeSH
• juvenilní hormony * metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktory bHLH metabolismus   genetika   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• juvenilní hormony * MeSH
• transkripční faktory bHLH MeSH

Acetamiprid is the only neonicotinoid registered in the European Union because the risks of neonicotinoids to honey bees and other pollinators are strictly regulated. Herein, we orally exposed honey bee colonies to sublethal concentrations of acetamiprid (20 μg/L) under isolated conditions. After one month of continuous exposure, the emerging bees and queens were collected and analyzed via high-throughput label-free quantitative proteomics using a data-independent acquisition strategy. Six and 34 significantly differentially expressed proteins (DEPs) were identified in the emerging bees and queens, respectively. Mrjp3 was the only DEP found in both sample types/castes, and its opposite regulation illustrated a differential response. The DEPs in the emerging bees (H/ACA RNP, Rap1GAP, Mrjp3, and JHE) suggested that sublethal exposure to acetamiprid affected cell cycle-related signaling, which may affect the life history of workers in the colony. The DEPs with increased levels in queens, such as Mrjps 1-4 and 6-7, hymenoptaecin, and apidaecin 22, indicated an activated immune response. Additionally, the level of farnesyl pyrophosphate synthase (FPPS), which is essential for the mevalonate pathway and juvenile hormone biosynthesis, was significantly decreased in queens. The impaired utilization of juvenile hormone in queens supported the identification of additional DEPs. Furthermore, the proteome changes suggested the existence of increased neonicotinoid detoxification by UDP-glucuronosyltransferase and increased amino acid metabolism. The results suggest that the continuous exposure of bee colonies to acetamiprid at low doses (nanograms per gram in feed) may pose a threat to the colonies. The different exposure routes and durations for the emerging bees and queens in our experiment must be considered, i.e., the emerging bees were exposed as larvae via feeding royal jelly and beebread provided by workers (nurse bees), whereas the queens were fed royal jelly throughout the experiment. The biological consequences of the proteomic changes resulting from sublethal/chronic exposure require future determination.

• Klíčová slova
• Acetamiprid, Apis mellifera, Chronic exposure, Insecticide, Pesticide risk assessment,
• MeSH
• insekticidy toxicita   MeSH
• juvenilní hormony * MeSH
• neonikotinoidy * toxicita   MeSH
• proteomika MeSH
• signální transdukce účinky léků   MeSH
• včely účinky léků   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetamiprid MeSH Prohlížeč
• insekticidy MeSH
• juvenilní hormony * MeSH
• neonikotinoidy * MeSH

To gain insights into how juvenile hormone (JH) came to regulate insect metamorphosis, we studied its function in the ametabolous firebrat, Thermobia domestica. Highest levels of JH occur during late embryogenesis, with only low levels thereafter. Loss-of-function and gain-of-function experiments show that JH acts on embryonic tissues to suppress morphogenesis and cell determination and to promote their terminal differentiation. Similar embryonic actions of JH on hemimetabolous insects with short germ band embryos indicate that JH's embryonic role preceded its derived function as the postembryonic regulator of metamorphosis. The postembryonic expansion of JH function likely followed the evolution of flight. Archaic flying insects were considered to lack metamorphosis because tiny, movable wings were evident on the thoraces of young juveniles and their positive allometric growth eventually allowed them to support flight in late juveniles. Like in Thermobia, we assume that these juveniles lacked JH. However, a postembryonic reappearance of JH during wing morphogenesis in the young juvenile likely redirected wing development to make a wing pad rather than a wing. Maintenance of JH then allowed wing pad growth and its disappearance in the mature juvenile then allowed wing differentiation. Subsequent modification of JH action for hemi- and holometabolous lifestyles are discussed.

• Klíčová slova
• developmental biology, differentiation, ecdysone, juvenile hormone, metamorphosis, myoglianin, precocene, thermobia domestica,
• MeSH
• biologická proměna * fyziologie   MeSH
• hmyz MeSH
• juvenilní hormony * MeSH
• morfogeneze MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• juvenilní hormony * MeSH

Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in reproduction. Here we investigated the role of these potent signaling molecules in embryonic germ cell development, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we observed active JH signaling first within and near primordial germ cells (PGCs) as they migrate to the developing gonad. Through in vivo and in vitro assays, we determined that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were decreased or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization of the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids have many roles in development and reproduction. We found that like JHs in Drosophila, RA was sufficient to impact mouse PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration.

• Klíčová slova
• Hmgcr, cell movement, embryonic development, gametogenesis, germ cells, gonad, juvenile hormones, ovary, retinoids, testis,
• MeSH
• Drosophila melanogaster * MeSH
• Drosophila MeSH
• gonády MeSH
• juvenilní hormony * MeSH
• lidé MeSH
• myši MeSH
• pohyb buněk MeSH
• savci MeSH
• terpeny MeSH
• zárodečné buňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• juvenilní hormony * MeSH
• terpeny MeSH

The corpora allata-corpora cardiaca (CA-CC) is an endocrine gland complex that regulates mosquito development and reproduction through the synthesis of juvenile hormone (JH). Epoxidase (Epox) is a key enzyme in the production of JH. We recently utilized CRISPR/Cas9 to establish an epoxidase-deficient (epox-/-) Aedes aegypti line. The CA from epox-/- mutants do not synthesize epoxidated JH III but methyl farneosate (MF), a weak agonist of the JH receptor, and therefore have reduced JH signalling. Illumina sequencing was used to examine the differences in gene expression between the CA-CC from wild type (WT) and epox-/- adult female mosquitoes. From 18,034 identified genes, 317 were significantly differentially expressed. These genes are involved in many biological processes, including the regulation of cell proliferation and apoptosis, energy metabolism, and nutritional uptake. In addition, the same CA-CC samples were also used to examine the microRNA (miRNA) profiles of epox-/- and WT mosquitoes. A total of 197 miRNAs were detected, 24 of which were differentially regulated in epox-/- mutants. miRNA binding sites for these particular miRNAs were identified using an in silico approach; they target a total of 101 differentially expressed genes. Our results suggest that a lack of epoxidase, besides affecting JH synthesis, results in the diminishing of JH signalling that have significant effects on Ae. aegypti CA-CC transcriptome profiles, as well as its miRNA repertoire.

• Klíčová slova
• Aedes aegypti, Corpora allata, Epoxidase, Juvenile hormone, Mosquito, RNA-Seq, Transcriptome, microRNA,
• MeSH
• Aedes * genetika   metabolismus   MeSH
• corpora allata metabolismus   MeSH
• exprese genu MeSH
• juvenilní hormony metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• juvenilní hormony MeSH
• mikro RNA * MeSH

Insect vitellogenins are an intriguing class of complex proteins. They primarily serve as a source of energy for the developing embryo in insect eggs. Vitellogenesis is a complex hormonally and neurally controlled process that command synthesis of vitellogenin molecules and ensures their transport from the female fat bodies or ovarial cells into eggs. The representatives of all insect hormones such as juvenile hormones, ecdysteroids, and neurohormones participate in vitellogenesis, but juvenile hormones (most insect species) and ecdysteroids (mostly Diptera) play the most important roles in the process. Strikingly, not only insect females, but also males have been reported to synthesize vitellogenins indicating their further utility in the insect body. Indeed, it has recently been found that vitellogenins perform a variety of biological functions in the insect body. They participate in defense reactions against entomopathogens such as nematodes, fungi, and bacteria, as well as against venoms such as the honeybee Apis mellifera venom. Interestingly, vitellogenins are also present in the venom of the honeybee itself, albeit their exact role is unknown; they most likely increase the efficacy of the venom in the victim's body. Within the bee's body vitellogenins contribute to the lifespan regulation as anti-aging factor acting under tight social interactions and hormonal control. The current minireview covers all of these functions of vitellogenins and portrays them as biologically active substances that play a variety of significant roles in both insect females and males, and not only acting as passive energy sources for developing embryo.

• MeSH
• ekdysteroidy * metabolismus   MeSH
• hmyz metabolismus   MeSH
• juvenilní hormony metabolismus   MeSH
• ovarium metabolismus   MeSH
• vitelogeniny * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ekdysteroidy * MeSH
• juvenilní hormony MeSH
• vitelogeniny * MeSH

Juvenile hormone (JH) controls the development and reproduction of insects. Therefore, a tight regulation of the expression of JH biosynthetic enzymes is critical. microRNAs (miRNAs) play significant roles in the post-transcriptional regulation of gene expression by interacting with complementary sequences in target genes. Previously, we reported that several miRNAs were differentially expressed during three developmental stages of Aedes aegypti mosquitoes with different JH levels (no JH, high JH, and low JH). One of these miRNAs was aae-miR-34-5p. In this study, we identified the presence of potential target sequences of aae-miR-34-5p in the transcripts of some genes encoding JH biosynthetic enzymes. We analysed the developmental expression patterns of aae-miR-34-5p and the predicted target genes involved in JH biogenesis. Increases in miRNA abundance were followed, with a delay, by decreases in transcript levels of target genes. Application of an inhibitor and a mimic of aae-miR-34-5p led respectively to increased and decreased levels of thiolase transcripts, which is one of the early genes of JH biosynthesis. Female adult mosquitoes injected with an aae-miR-34-5p inhibitor exhibited significantly increased transcript levels of three genes encoding JH biosynthetic enzymes, acetoacetyl-CoA thiolase (thiolase), farnesyl diphosphate phosphatase, and farnesal dehydrogenase. Overall, our results suggest a potential role of miRNAs in JH production by directly targeting genes involved in its biosynthesis.

• MeSH
• Aedes * MeSH
• juvenilní hormony metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• juvenilní hormony MeSH
• mikro RNA * MeSH