Juvenile hormone resistance: ! no PASaran !

Abstract

The control of growth, differentiation, metamorphosis, and reproduction in insects is a complex interplay of hormones, with the steroid hormone ecdysone and the sesquiterpenoid juvenile hormone (JH) playing major roles. Molting is controlled by ecdysone, and the type of molt is controlled by JH. The presence of JH maintains the insect in the juvenile (larval) state, hence its name (1), and the relative absence of JH allows metamorphosis to proceed. With the discovery of insect JH came the idea that application of JH or its agonists at an inopportune time, when the insect required the absence of JH for metamorphosis—the “Achilles’ heel” of insect development—would disrupt this complex endocrine machinery. Analogs of JH, developed since the 1970s and euphemistically called “insect growth regulators,” are now among the most environmentally friendly types of insecticides. These chemicals, including methoprene, pyriproxyfen, and fenoxycarb, proved to be excellent mimics of the natural hormone, but, paradoxically, the molecular mode of action of JH has remained very much a mystery (2, 3). Now, studies on the insect’s response to these powerful chemicals—resistance—provide a direct avenue into the mode of action of JH itself. Ashok et al. (4) report in the current issue of the Proceedings the identity of the Methoprene-tolerant gene of Drosophila melanogaster as a member of the bHLH-PAS family of transcriptional regulators. This significant advance raises many questions, and its implications will be discussed here. Selection for methoprene-resistant mutants in D. melanogaster led to the definition of a genetic locus, Methoprene-tolerant or Met (5). Flies carrying the Met alleles are up to 100-fold resistant to structurally diverse JH analogs and to JH itself. The Met flies are not only resistant to the lethal effects of JH, but also to all the more subtle morphogenetic signs of hormone excess. For instance, treatment with methoprene …