A new paradigm in insect development and metamorphosis: Multiple farnesoid hormones with independent receptors

The long-established paradigm of insect metamorphosis is that the evolution of insect metamorphosis was occasioned by the advent of a new signaling pathway for “juvenile hormone” (methyl epoxyfarnesoate, JH). While the lower Crustacea methyl farnesoate is the only farnesoid biosynthesized and released into circulation, the long prevailing paradigm has held that methyl farnesoate is but a synthetic precursor to the ‘active’ JH that is released into circulation. The results of our recent studies of both hemimetabolous and holometabolous insects (including Orthoptera, Hemiptera, Hymenoptera and Diptera) challenge this paradigm. Our studies prompt the consideration of a new paradigm in which multiple physiologically farnesoid compounds are biosynthesized and released into circulation. Under this new evidence-based paradigm, farnesoid-specific nuclear hormone receptors exist, which bind to their cognate ligand with nanomolar affinity, and the relative ratios of the circulating farnesoids to each other fluctuate dramatically during insect development. Supported in part by NIH.