Barbara B. Jones and Martin Petkovich Pages 155 - 168 ( 14 )
It has long been known that the structural modification of steroid hormones can alter their biological activity. Some of these changes in activity are attributable to altered uptake and metabolism. With the cDNA cloning and characterization of nuclear receptors for steroids and related compounds, it has become possible to ascribe changes in ligand activity to specific alterations in receptor function. In this review we will discuss the steroid/thyroid hormone receptor superfamily, and how knowledge of receptor structures and mechanism of action may be exploited therapeutically to alter their effects on gene expression in human disease states. We will discuss the basic structure of nuclear receptors and possible mechanisms by which their activities can be altered by ligands, both natural and synthetic. Later, we will focus on specific investigations related to the mechanism of action of some of the more widely studied antagonists. Finally we will examine the use of synthetic ligands and look at how determination of detailed receptor structures may help us to design more highly specific and effective ligands.