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.