Tissue-specific expression and regulation of the mineralocorticoid receptor during development

This review summarizes current knowledge on the mineralocorticoid receptor (MR), a nuclear receptor encoded by the NR3C2 gene, and its ligand aldosterone. In epithelial tissues, such as the kidney, colon, salivary glands, and skin, particularly within the sweat glands, the MR plays a key role in regulating sodium reabsorption. In non-epithelial tissues, such as the brain, adipose tissue, and heart, glucocorticoids are the main physiological MR ligands due to the absence of the 11β-hydroxysteroid dehydrogenase type 2. MR expression begins during development with tissue-specific patterns. In the kidney, MR levels peak mid-gestation, decrease at birth, and then increase postnatally. Loss of MR function, as observed in pseudohypoaldosteronism type 1 causes salt-wasting syndrome. Similar patterns are seen in the heart and brain, especially the hippocampus, where it influences stress regulation. On the contrary, MR expression is maintained at birth in the lung for neonatal fluid clearance via epithelial sodium channels. It is also present in tissues such as skin, retina, and gastrointestinal tract, indicating broad physiological roles. MR expression during fetal development correlates with adaptations to extra-uterine life, such as changes in amniotic fluid osmolality and aldosterone levels. MR gene expression and activity are tightly regulated through multiple mechanisms. These include transcriptional control via two promoters, post-transcriptional regulation involving RNA-binding proteins and microRNAs, and post-translational modifications, such as phosphorylation, sumoylation, and ubiquitination. These regulatory levels ensure appropriate MR function across different tissues and developmental stages and may have implications for conditions such as hypertension and heart failure.