Juvenile hormone (JH), a sesquiterpenoid produced by the insect corpus allatum gland (CA), is a key regulator of insect metamorphosis, reproduction, caste differentiation, and polyphenism. The first part of JH biosynthesis occurs via the universal eukaryotic mevalonate pathway. The final steps involve epoxidation and methylation. However, the sequence of these steps might not be conserved among all insects and Crustacea. Therefore, we used available genomic and transcriptomic data and identified JH acid methyltransferase (JHAMT), analyzed their genomic duplications in selected model organisms, and reconstructed their phylogeny. We have further reconstructed phylogeny of FAMeT proteins and show that evolution of this protein group is more complicated than originally appreciated. The analysis delineates important milestones in the evolution of several JH biosynthetic enzymes in arthropods, reviews major literature data on the last steps of JH synthesis, and defines questions and some hypotheses worth pursuing experimentally.

• Klíčová slova
• Alternative splicing, Epoxidase, Evolution, Gene duplication, Juvenile hormone, Methyl transferase,
• MeSH
• corpora allata MeSH
• hmyz genetika   metabolismus   MeSH
• hmyzí proteiny metabolismus   MeSH
• juvenilní hormony * metabolismus   MeSH
• seskviterpeny * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hmyzí proteiny MeSH
• juvenilní hormony * MeSH
• seskviterpeny * MeSH

Juvenile hormone (JH) signalling provides vital regulatory functions during insect development via transcriptional regulation of genes critical for the progression of metamorphosis and oogenesis. Despite the importance of JH signalling, the underlying molecular mechanisms remain largely unknown. Our current understanding of the pathway depends on static end-point information and suffers from the lack of time-resolved data. Here, we have addressed the dynamic aspect of JH signalling by monitoring in real time the interactions of insect JH receptor proteins. Use of two tags that reconstitute a functional luciferase when in proximity enabled us to follow the rapid assembly of a JH receptor heterodimer from basic helix-loop-helix/Per-Arnt-SIM (bHLH-PAS) proteins, methoprene-tolerant (Met) and taiman (Tai), upon specific JH binding to Met. On a similar timescale (minutes), the dissociation of Met-Met complexes occurred, again strictly dependent on Met interaction with specific agonist ligands. To resolve questions regarding the regulatory role of the chaperone Hsp90/83 in the JHR complex formation, we used the same technique to demonstrate that the Met-Hsp83 complex persisted in the agonist absence but readily dissociated upon specific binding of JH to Met. Preincubation with the Hsp90 inhibitor geldanamycin showed that the chaperone interaction protected Met from degradation and was critical for Met to produce the active signalling dimer with Tai. Thus, the JH receptor functions appear to be governed by principles similar to those regulating the aryl hydrocarbon receptor, the closest vertebrate homologue of the arthropod JH receptor.

• Klíčová slova
• Hsp90, bHLH-PAS domain, dimerisation, hormone receptor, juvenile hormone,
• MeSH
• juvenilní hormony * metabolismus   MeSH
• ligandy MeSH
• methopren * farmakologie   metabolismus   MeSH
• molekulární chaperony metabolismus   MeSH
• regulace genové exprese MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• juvenilní hormony * MeSH
• ligandy MeSH
• methopren * MeSH
• molekulární chaperony MeSH

Juvenile hormone (JH), synthesized by the corpora allata (CA), controls development and reproduction in mosquitoes through its action on thousands of JH-responsive genes. These JH-dependent processes can be studied using tools that increase or decrease JH titers in vitro and in vivo. Juvenile hormone acid methyl transferase (JHAMT) is a critical JH biosynthetic enzyme. JHAMT utilizes the methyl donor S-adenosyl-methionine (SAM) to methylate farnesoic acid (FA) into methyl farnesoate (MF), releasing the product S-adenosyl-L-homocysteine (AdoHcy), which inhibits JHAMT. S-adenosyl-homocysteine hydrolase (SAHH) catalyzes AdoHcy hydrolysis to adenosine and homocysteine, alleviating AdoHcy inhibition of JHAMT. 3-deazaneplanocin A (DZNep), an analog of adenosine, is an inhibitor of SAHH, and an epigenetic drug for cancer therapy. We tested the effect of DZNep on in vitro JH synthesis by CA of mosquitoes. DZNep inhibited JH synthesis in a dose-response fashion. Addition of MF, but not of FA relieved the inhibition, demonstrating a direct effect on JHAMT. In vivo experiments, with addition of DZNep to the sugar ingested by mosquitoes, resulted in a dose-response decrease in JH synthesis and JH hemolymphatic titers, as well as expression of early trypsin, a JH-dependent gene. Our studies suggest that DZNep can be employed to lower JH synthesis and titer in experiments evaluating JH-controlled processes in mosquitoes.

• Klíčová slova
• Aedes aegypti, Corpora allata, DZNep, Early trypsin, Inhibition, Juvenile hormone synthesis, Methyltransferase, Titer,
• MeSH
• adenosin aplikace a dávkování   analogy a deriváty   MeSH
• Aedes genetika   metabolismus   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• juvenilní hormony biosyntéza   MeSH
• methyltransferasy genetika   metabolismus   MeSH
• metylace MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 3-deazaneplanocin MeSH Prohlížeč
• adenosin MeSH
• hmyzí proteiny MeSH
• juvenile hormone acid methyl transferase, Aedes aegypti MeSH Prohlížeč
• juvenilní hormony MeSH
• methyltransferasy MeSH

The efficacy of juvenile hormone III (JH III) and two JH-mimicking compounds was compared in laboratory experiments with Reticulitermes lucifugus (Rossi), R. santonensis Feytaud and R. virginicus (Banks). Induction of presoldier, soldier and/or soldier-worker intercaste differentiation was taken as positive response to the treatment. The novel juvenogen, a fatty acid ester of a juvenoid alcohol, induced greatest soldier differentiation in all species tested, followed by hydroprene. JH III was less effective. Representatives of three Reticulitermes species showed similar trends in soldier induction rates. Differences in mortality in treatments of termites of the same species from different colonies with the same compound were observed and evidently were caused by differences in the conditions of respective colonies.

• MeSH
• biologická kontrola škůdců MeSH
• insekticidy farmakologie   MeSH
• Isoptera účinky léků   růst a vývoj   MeSH
• juvenilní hormony farmakologie   MeSH
• morfogeneze účinky léků   MeSH
• nenasycené mastné kyseliny farmakologie   MeSH
• seskviterpeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• ethyl-3,7,11-trimethyl-2,4-dodecadienoate MeSH Prohlížeč
• insekticidy MeSH
• juvenile hormone III MeSH Prohlížeč
• juvenilní hormony MeSH
• nenasycené mastné kyseliny MeSH
• seskviterpeny 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

Triatomines are vectors of Chagas disease and important model organisms in insect physiology. "Kissing bugs" are obligatory hematophagous insects. A blood meal is required to successfully complete oogenesis, a process primarily controlled by juvenile hormone (JH). We used Dipetalogaster maxima as an experimental model to further understand the roles of JH in the regulation of vitellogenesis and oogenesis. A particular focus was set on the role of JH controlling lipid and protein recruitment by the oocytes. The hemolymph titer of JH III skipped bisepoxide increased after a blood meal. Following a blood meal there were increased levels of mRNAs in the fat body for the yolk protein precursors, vitellogenin (Vg) and lipophorin (Lp), as well as of their protein products in the hemolymph; mRNAs of the Vg and Lp receptors (VgR and LpR) were concomitantly up-regulated in the ovaries. Topical administration of JH induced the expression of Lp/LpR and Vg/VgR genes, and prompted the uptake of Lp and Vg in pre-vitellogenic females. Knockdown of the expression of LpR by RNA interference in fed females did not impair the Lp-mediated lipid transfer to oocytes, suggesting that the bulk of lipid acquisition by oocytes occurred by other pathways rather than by the endocytic Lp/LpR pathway. In conclusion, our results strongly suggest that JH signaling is critical for lipid storage in oocytes, by regulating Vg and Lp gene expression in the fat body as well as by modulating the expression of LpR and VgR genes in ovaries.

• Klíčová slova
• Endocytic receptors, Juvenile hormone, Lipid metabolism, Lipophorin, Oogenesis, Triatomine,
• MeSH
• hmyz metabolismus   fyziologie   MeSH
• hmyzí proteiny metabolismus   MeSH
• juvenilní hormony metabolismus   MeSH
• lipoproteiny metabolismus   MeSH
• metabolismus lipidů * MeSH
• oocyty metabolismus   MeSH
• oogeneze fyziologie   MeSH
• ovarium metabolismus   MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• RNA interference MeSH
• signální transdukce MeSH
• Triatominae * metabolismus   fyziologie   MeSH
• vitelogeneze fyziologie   MeSH
• vitelogeniny metabolismus   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
• hmyzí proteiny MeSH
• juvenilní hormony MeSH
• lipophorin receptor MeSH Prohlížeč
• lipophorin MeSH Prohlížeč
• lipoproteiny MeSH
• receptory cytoplazmatické a nukleární MeSH
• vitelogeniny MeSH

Synthetic compounds that mimic the action of juvenile hormones (JHs) are founding members of a class of insecticides called insect growth regulators (IGRs). Like JHs, these juvenoids block metamorphosis of insect larvae to reproductive adults. Many biologically active juvenoids deviate in their chemical structure considerably from the sesquiterpenoid JHs, raising questions about the mode of action of such JH mimics. Despite the early deployment of juvenoid IGRs in the mid-1970s, their molecular effect could not be understood until recent discoveries of JH signaling through an intracellular JH receptor, namely the ligand-binding transcription factor Methoprene-tolerant (Met). Here, we briefly overview evidence defining three widely employed and chemically distinct juvenoid IGRs (methoprene, pyriproxyfen, and fenoxycarb), as agonist ligands of the JH receptor. We stress that knowledge of the target molecule is critical for using these compounds both as insecticides and as research tools.

• Klíčová slova
• Drosophila, IGR, agonist ligand, bHLH-PAS protein, hormone receptor, juvenile hormone,
• MeSH
• biologická proměna účinky léků   MeSH
• fenylkarbamáty metabolismus   farmakologie   MeSH
• insekticidy chemie   metabolismus   farmakologie   MeSH
• juvenilní hormony agonisté   chemie   farmakologie   MeSH
• ligandy MeSH
• methopren metabolismus   farmakologie   MeSH
• pyridiny metabolismus   farmakologie   MeSH
• rezistence k insekticidům MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fenoxycarb MeSH Prohlížeč
• fenylkarbamáty MeSH
• insekticidy MeSH
• juvenilní hormony MeSH
• ligandy MeSH
• methopren MeSH
• pyridiny MeSH
• pyriproxyfen MeSH Prohlížeč

The effect of the topical application of the synthetic juvenile hormone JH-I on adult specimens of Musca domestica vicina Macq was studied. The adult stage responded to different JH-I concentrations in different ways. The gonotrophic cycle was shortened, the number of eggs decreased and the hatching rate was reduced. The adults of the next generation displayed a number of anomalies. The ovarian amino acid concentrations varied considerably according to the dose of JH-I and the stage of maturation of the relevant ovary.

• MeSH
• juvenilní hormony farmakologie   MeSH
• moucha domácí účinky léků   MeSH
• ovarium účinky léků   MeSH
• seskviterpeny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• juvenile hormone I MeSH Prohlížeč
• juvenilní hormony MeSH
• seskviterpeny MeSH

Methyl farnesoate (MF) plays hormonal regulatory roles in crustaceans. An epoxidated form of MF, known as juvenile hormone (JH), controls metamorphosis and stimulates reproduction in insects. To address the evolutionary significance of MF epoxidation, we generated mosquitoes completely lacking either of the two enzymes that catalyze the last steps of MF/JH biosynthesis and epoxidation, respectively: the JH acid methyltransferase (JHAMT) and the P450 epoxidase CYP15 (EPOX). jhamt-/- larvae lacking both MF and JH died at the onset of metamorphosis. Strikingly, epox-/- mutants, which synthesized MF but no JH, completed the entire life cycle. While epox-/- adults were fertile, the reproductive performance of both sexes was dramatically reduced. Our results suggest that although MF can substitute for the absence of JH in mosquitoes, it is with a significant fitness cost. We propose that MF can fulfill most roles of JH, but its epoxidation to JH was a key innovation providing insects with a reproductive advantage.

• Klíčová slova
• Aedes aegypti, corpora allata, juvenile hormone, methyl farnesoate, reproduction,
• MeSH
• Aedes enzymologie   genetika   MeSH
• biologická proměna MeSH
• genetická zdatnost * MeSH
• juvenilní hormony biosyntéza   MeSH
• molekulární evoluce * MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• rozmnožování MeSH
• seskviterpeny metabolismus   MeSH
• sexuální chování zvířat MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• 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
• methyl farnesoate MeSH Prohlížeč
• nenasycené mastné kyseliny MeSH
• seskviterpeny MeSH

The molecular action of juvenile hormone (JH), a regulator of vital importance to insects, was until recently regarded as a mystery. The past few years have seen an explosion of studies of JH signaling, sparked by a finding that a JH-resistance gene, Methoprene-tolerant (Met), plays a critical role in insect metamorphosis. Here, we summarize the recently acquired knowledge on the capacity of Met to bind JH, which has been mapped to a particular ligand-binding domain, thus establishing this bHLH-PAS protein as a novel type of an intracellular hormone receptor. Next, we consider the significance of JH-dependent interactions of Met with other transcription factors and signaling pathways. We examine the regulation and biological roles of genes acting downstream of JH and Met in insect metamorphosis. Finally, we discuss the current gaps in our understanding of JH action and outline directions for future research.

• MeSH
• biologická proměna MeSH
• hmyz genetika   růst a vývoj   metabolismus   MeSH
• juvenilní hormony genetika   metabolismus   MeSH
• methopren metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• juvenilní hormony MeSH
• methopren MeSH
• transkripční faktory MeSH