Phosphoinositide-derived messengers in endocrine signaling

One of the fundamental questions in endocrinology is how circulating or locally produced hormones affect target cell functions by activating specific receptors linked to numerous signal-transduction pathways. An important subset of G protein-coupled cell-surface receptors can activate phospholipase C enzymes to hydrolyze a small but critically important class of phospholipids, the phosphoinositides. Although this signaling pathway has been extensively explored over the last 20 years, this has proven to be only the tip of the iceberg, and the multiplicity and diversity of the cellular functions controlled by phosphoinositides have surpassed any imagination. Phosphoinositides have been found to be key regulators of ion channels and transporters, and controllers of vesicular trafficking and the transport of lipids between intracellular membranes. Essentially, they organize the recruitment and regulation of signaling protein complexes in specific membrane compartments. While many of these processes have been classically studied by cell biologists, molecular endocrinology cannot ignore these recent advances, and now needs to integrate the cell biologist's views in the modern concept of how hormones affect cell functions and how derailment of simple molecular events can lead to complex endocrine and metabolic disorders.