ALDOSTERONE RECEPTORS - NEW INSIGHTS IN TRANSDUCTION PATHWAYS OF HORMONAL SIGNAL

Aldosterone exerts its effects by binding to an intracellular receptor , the mineralocorticoid receptor (MR), that belongs to the superfamily of ligand-regulated transcription factors. This family includes recep tors for steroid and thyroid hormones, vitamin D and retinoids and als o orphan receptors with unidentified ligands. All the members of this family display a modular structure composed of a transactivation domai n, a DNA binding domain and a ligand binding domain. Upon hormone bind ing, the receptor undergoes a series of structural modifications leadi ng to its interaction with DNA sequences and transcriptional modulatio n of specific genes. Since the level of circulating glucocorticoids is 100-1000 fold higher than that of aldosterone and the affinity of the MR is identical for glucocorticoids and aldosterone, the question of the mechanisms responsible for the in vivo selectivity of aldosterone for its receptor arises. The mechanisms of cellular and tissular selec tivity involved in the physiological response of aldosterone are discu ssed in this review.