Ecdysteroids

Ecdysteroid: member of a class of polyhydroxylated steroids found in invertebrate animals (zooecdysteroids; moulting hormones), plants (phytoecdysteroids) and fungi (mycoecdysteroids). Over 500 structural analogues are currently known. Biosynthetically, they derive from C27-, C28- or C29-sterols. The most frequently encountered analogue (in arthropods and plants) is 20-hydroxyecdysone (2β,3β,14α, 20R,22R,25-hexahydroxycholest-7-en-6-one). In arthropods, ecdysteroids occur universally and regulate development by inducing moulting and reproduction, where their action is mediated by high-affinity binding to an intracellular member of the class of nuclear receptor (NR) proteins (ecdysteroid receptor; EcR) dimerised with a second NR (USP/RxR). This receptor complex binds to specific DNA promoter sites and regulates gene expression. In plants, ecdysteroids are a class of secondary compounds, occurring in varying amounts in certain species, but not all in others. Phytoecdysteroids are believed to contribute to the reduction of invertebrate predation by acting as feeding deterrents or endocrine disruptors. Ecdysteroids also possess a wide range of positive pharmacological effects in mammals, where the mode of action involves moderate-affinity binding to plasma-membrane-bound receptors and not interaction with the classical NRs for vertebrate steroid hormones.

Halloween genes in panarthropods and the evolution of the early moulting pathway in Ecdysozoa

Moulting is a characteristic feature of Ecdysozoa—the clade of moulting animals that includes the hyperdiverse arthropods and less speciose groups, such as onychophorans, tardigrades and nematodes. Moulting has been best analysed in arthropods, specifically in insects and crustaceans, in which a complex neuroendocrine system acts at the genomic level and initiates the transcription of genes responsible for moulting. The key moulting hormones, ecdysone and 20-hydroxyecdysone, are subsequently synthesized from cholesterol ingested with food. Their biosynthesis is regulated by the Rieske-domain protein Neverland and cytochrome P450 enzymes encoded by the so-called ‘Halloween’ genes. Ecdysone is then released into the haemolymph and modified into 20-hydroxyecdysone, which binds to the nuclear receptor EcR/USP and initiates transcription of the Early genes. As little is known about the moulting pathway of other ecdysozoans, we examined the occurrence of genes involved in ecdysteroid biosynthesis and the early moulting cascade across ecdysozoan subgroups. Genomic and transcriptomic searches revealed no Halloween genes in cycloneuralians, whereas only shadow ( CYP315A1 ) is present in onychophorans and tardigrades, suggesting that the Halloween genes evolved stepwise in panarthropods. These findings imply that the genes which were responsible for the ecdysteroid biosynthesis in the last common ancestor of Ecdysozoa are currently unknown.

Ecdysteroid Profiles of Two Ajuga species, A. iva and A. remota

Phytoecdysteroids are plant analogues of insect moulting hormones and are used by plants to repel or disturb phytophagous insects. They are also active on mammals and present in many plants used in traditional medicine. The Ajuga genus contains several such species, which occur in various pharmacopoeias. We report the isolation and identification of major and minor ecdysteroids present in two Ajuga species, A. iva and A. remota, both of which are used as medicinal plants in Africa. Three minor ecdysteroids (abutasterone, ponasterone A and sidisterone) have been found for the first time in the Ajuga genus.

Regulation of ecdysteroid signalling during Drosophila development: identification, characterization and modelling of ecdysone oxidase, an enzyme involved in control of ligand concentration

The steroidal moulting hormones (ecdysteroids) mediate developmental transitions in insects, and their regulation is mainly controlled by the production and inactivation of these steroid hormones at the appropriate developmental times. One route of metabolism of ecdysteroids in insects involves EO (ecdysone oxidase)-catalysed conversion into 3-dehydroecdysteroid, which undergoes reduction to the corresponding 3-epiecdysteroid. By a twin-stranded bioinformatics approach, employing both phylogenomics and model structure-based analysis, we first predicted that DmEO (the EO of Drosophila melanogaster) corresponds to the protein product of gene CG9504. When CG9504 was expressed in COS7 cells, significant conversion of ecdysone into 3-dehydroecdysone was observed. Quantitative PCR and enzyme assay showed that DmEO was mainly expressed in the midgut during the late instars at a time corresponding to a hormone titre peak. DmEO shares only 27% amino acid sequence identity with Spodoptera littoralis (Lepidoptera) EO, yet key substrate-binding residues are well conserved. A model of DmEO is consistent with an inability to catalyse reaction of cholesterol derivatives. The significance of DmEO in ligand activation is discussed in relation to new evidence suggesting that 3-dehydro- and 3-epiecdysteroids may be functionally active as ligands in a novel, atypical ecdysteroid signalling pathway involving the Drosophila orphan nuclear receptor, DHR38, rather than being merely hormone inactivation products.

Hormonal control of tick development and reproduction

Ecdysteroids (moulting hormones), juvenoids and neuropeptides in ticks are reviewed but, by far, the emphasis is on the former since this class of hormones has been the subject of most investigations. In immature stages of ticks, ecdysteroids have been shown to regulate moulting and to terminate larval diapause. Although there is a paucity of information on the molecular action of ecdysteroids in ticks, their action appears to be via a heterodimeric ecdysone/ultraspiracle receptor, as in insects. The role of ecdysteroids in sperm maturation in adult males is considered. In females, ecdysteroids function in the regulation of salivary glands, of production of sex pheromones and of oogenesis and oviposition. There is evidence for ecdysteroid production in the integument and pathways of hormone inactivation are similar to those in insects. Ecdysteroids also function in embryogenesis. Although evidence for the occurrence and functioning of juvenile hormones in ticks has been contradictory, in recent thorough work it has not been possible to detect known juvenile hormones in ticks, nor to demonstrate effects of extracts on insects. Factors (neuropeptides) from the synganglion affect physiological processes and limited immunocytochemical studies are reviewed. Sigificantly, a G-protein-coupled receptor has been cloned, expressed, and specifically responds to myokinins.