title: Ecdysone agonists: mechanism and importance in controlling insect pests of agriculture and forestry.
abstract: Molting is the result of the expression of a cascade of genes that is sequentially both up and down-regulated by the molting hormone, 20-hydroxyecdysone (20E), which is secreted as a pulse during each instar. Benzoyl hydrazine analogs of 20E act like the native molting hormone at the molecular level by binding with the ecdysone receptor complex and transactivating a succession of molt initiating transcription factors that, in turn, induce the expression of a group of molt-related genes. As a result of the expression of these up-regulated genes, the larva undergoes apolysis and head capsule slippage and takes on the appearance of the pharate larva. However, unlike 20E, which is cleared at this juncture, allowing the down-regulated genes to be expressed, these synthetic analogs bind strongly to the receptors and remain in place and repress all the down-regulatory genes such as the ones necessary for cuticle elaboration, sclerotization, and ecdysis resulting in a developmental arrest in this state. As a result, the treated larva goes into a precocious incomplete molt that is lethal. Two of the analogs, tebufenozide and methoxyfenozide, are lepidopteran specific and have good control potential for open feeding larvae that ingest this material while a third one, halofenozide, acts on coleopteran larvae. Since they specifically act through an insect receptor complex, they have little or no effect on non-target species, making them environmentally attractive pest control agents. Some insects, however, show resistance to these analogs and this could be, inter alia, due to an ATP Binding Cassette Transporter like system that selectively pumps out the analogs.
authors.affiliation: Great Lakes Forestry Center, Canadian Forest Service, Sault Ste. Marie, Ontario, Canada. aretnak@nrcan.gc.ca
authors.forename: Arthur
authors.initials: A
authors.lastname: Retnakaran
authors.forename: Peter
authors.initials: P
authors.lastname: Krell
authors.forename: Qili
authors.initials: Q
authors.lastname: Feng
authors.forename: Basil
authors.initials: B
authors.lastname: Arif
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000383:Agriculture; D000818:Animals; D002460:Cell Line; D004440:Ecdysone / Q000819:agonists*; D004441:Ecdysterone / Q000235:genetics / Q000378:metabolism; D016468:Forestry; D015870:Gene Expression / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D007305:Insecticide Resistance / Q000187:drug effects / Q000502:physiology; D007814:Larva / Q000187:drug effects / Q000502:physiology; D007915:Lepidoptera / Q000502:physiology*; D008675:Metamorphosis, Biological / Q000502:physiology; D018978:Molting / Q000187:drug effects / Q000502:physiology; D010572:Pest Control, Biological / Q000379:methods*; D010641:Phenotype
chemical_list: D018528:ATP-Binding Cassette Transporters; D006834:Hydrazines; D004440:Ecdysone; D004441:Ecdysterone; C082026:tebufenozide