The molecular site of action of juvenile hormone and juvenile hormone insecticides during metamorphosis: how these compounds kill insects

Studies in a variety of insects during the past four decades has deepened our understanding of juvenile hormone (JH) physiology, but how this hormone works at the molecular level remains elusive. Similarly, the mechanism of toxicity of JH analogue insecticides is still in question. There is much evidence from laboratory usage that JHAs act as JH agonists and generally show the highest toxicity when applied at the onset of metamorphosis. A physiological basis for the toxicity and morphogenetic effects has been suggested by recent work linking these effects with interference with the expression or action of certain genes, particularly the Broad-Complex (BR-C) transcription factor gene, that direct metamorphic change. Misexpressed BR-C then leads to improper expression of one or more downstream effector genes controlled by BR-C gene products, resulting in abnormal developmental and physiological changes that disrupt metamorphosis. Therefore, JH is a necessary molecule at certain times in insect development but becomes toxic when present during metamorphosis.