Metabolic conversion as a pre-receptor control mechanism for lipophilic hormones

The majority of physiological effects mediated by steroids, retinoids and t hyroids is accomplished by binding to members of the nuclear receptor super family of ligand activated transcription factors. The complex specific effe cts of lipid hormones depend not only on receptor expression, distribution and interactions, but also on the availability and metabolic conversion of the hormone itself. The cell-specific metabolic activation of inactive horm one precursors introduces a further level of hormonal regulation, and const itutes an important concept in endocrinology. The metabolic reactions carri ed out are achieved by dehydrogenases/reductases, hydroxylases and other en zymes, acting on ligands of the steroid/thyroid/retinoic hormone receptor s uperfamily. The concept implies that these tissue- and cell-specific metabo lic conversions contribute to lipid hormone action, thus pointing to novel targets in drug development. All components of this signalling system, the hormone compounds, the receptor proteins, and modifying enzyme families ori ginate from an early metazoan date, emphasizing the essential nature of all elements for development and diversification of vertebrate life.