A perspective for understanding the modes of juvenile hormone action as a lipid signaling system

The juvenile hormones of insects regulate an unusually large diversity of processes during postembryonic development and adult reproduction. It is a long-standing puzzle in insect developmental biology and physiology how one hormone can have such diverse effects. The search for molecular mechanisms of juvenile hormone action has been guided by classical models for hormone-receptor interaction. Yet, despite substantial effort, the search for a juvenile hormone receptor has been frustrating and has yielded limited results. We note here that a number of lipid-soluble signaling molecules in vertebrates, invertebrates and plants show curious similarities to the properties of juvenile hormones of insects. Until now, these signaling molecules have been thought of as uniquely evolved mechanisms that perform specialized regulatory functions in the taxon where they were discovered. We show that this array of lipid signaling molecules share interesting properties and suggest that they constitute a large set of signal control and transduction mechanisms that include, but range far beyond, the classical steroid hormone signaling mechanism. Juvenile hormone is the insect representative of this widespread and diverse system of lipid signaling molecules that regulate protein activity in a variety of ways. We propose a synthetic perspective for understanding juvenile hormone action in light of other lipid signaling systems and suggest that lipid activation of proteins has evolved to modulate existing signal activation and transduction mechanisms in animals and plants. Since small lipids can be inserted into many different pathways, lipid-activated proteins have evolved to play a great diversity of roles in physiology and development.