Nuclear steroid receptors in apoptosis

Abstract

Nuclear steroid receptors (NSR) are ligand-activated transcription factors that play key roles in a variety of vital physiological phenomena including developmental or endocrine signaling, reproduction, and homeostasis. In addition, they are also implicated in other important biological processes, such as apoptosis. Modulation of apoptosis by NSR is mostly associated with control of gene expression, and includes both induction and prevention of apoptosis depending on cell type. Of note, recently described nongenomic mechanisms of NSR, in particular glucocorticoid receptor translocation to mitochondria, were suggested to be crucial steps for triggering apoptosis. NSR oft en act solely as nuclear transporters of other regulatory molecules, thus indirectly regulating several apoptosis-related genes. Curiously, NSR are thought to cooperate with the antiapoptotic endogenous bile acid, ursodeoxycholic acid, to prevent programmed cell death. The huge diversity of natural ligands and xenobiotics that bind to NSR and regulate their function makes NSR one of the most exciting drug targets for potential therapeutic application. The next decade will almost certainly unveil the remarkable role of NSR in modulating the life and death struggle of cells and organ systems in human health and disease.