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Local Control of Aldosterone Production and Primary Aldosteronism

2016; Elsevier BV; Volume: 27; Issue: 3 Linguagem: Inglês

10.1016/j.tem.2016.01.003

1879-3061

Enzo Lalli, Jacques Barhanin, Maria‐Christina Zennaro, Richard Warth,

Cardiovascular, Neuropeptides, and Oxidative Stress Research

Primary aldosteronism (PA) is the most common form of endocrine hypertension. Patients with PA exhibit more severe cardiovascular damage than patients with essential hypertension. The most common cause of PA is a benign aldosterone-producing adenoma (APA) of the adrenal cortex. Local mechanisms controlling aldosterone production in the adrenal cortex are particularly relevant in the pathogenesis of PA. In APA, somatic mutations are present that induce increased cytosolic calcium activity and consequent activation of aldosterone production. Recent data show that nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a two-hit model for APA formation. Remarkably, somatic mutations in the same genes that are mutated in APA are also found in cell clusters producing aldosterone in normal adrenal. Primary aldosteronism (PA) is caused by excessive production of aldosterone by the adrenal cortex and is determined by a benign aldosterone-producing adenoma (APA) in a significant proportion of cases. Local mechanisms, as opposed to circulatory ones, that control aldosterone production in the adrenal cortex are particularly relevant in the physiopathological setting and in the pathogenesis of PA. A breakthrough in our understanding of the pathogenetic mechanisms in APA has been the identification of somatic mutations in genes controlling membrane potential and intracellular calcium concentrations. However, recent data show that the processes of nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a model envisaging different molecular events for the pathogenesis of APA. Primary aldosteronism (PA) is caused by excessive production of aldosterone by the adrenal cortex and is determined by a benign aldosterone-producing adenoma (APA) in a significant proportion of cases. Local mechanisms, as opposed to circulatory ones, that control aldosterone production in the adrenal cortex are particularly relevant in the physiopathological setting and in the pathogenesis of PA. A breakthrough in our understanding of the pathogenetic mechanisms in APA has been the identification of somatic mutations in genes controlling membrane potential and intracellular calcium concentrations. However, recent data show that the processes of nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a model envisaging different molecular events for the pathogenesis of APA. a steroid hormone produced in the adrenal zona glomerulosa that has a major role in the regulation of plasma volume and ion homeostasis. It activates the mineralocorticoid receptor that regulates target gene expression. a benign tumor of the adrenal cortex that produces aldosterone. they are groups of cells in the normal adrenal cortex that are present in the zona glomerulosa and extend centripetally in the zona fasciculata and that express aldosterone synthase. ion channels with selectivity for potassium. They play a pivotal role in regulating membrane potential and intracellular calcium concentration in adrenocortical cells. cAMP-regulated protein signaling pathway that is essential in regulating growth and steroid hormone production in the adrenal cortex. the proteolytic enzyme renin cleaves the plasma precursor angiotensinogen to angiotensin I, from which angiotensin II (Ang II) is made through subsequent cleavage by angiotensin-converting enzyme (ACE). Ang II has a vasoconstrictor effect and increases aldosterone production from the adrenal cortex. a conserved developmental pathway with an important role in regulating cell differentiation in the adrenal cortex. another conserved signaling pathway that has a major role in development and in tissue homeostasis and renewal. It involves stabilization and nuclear translocation of the membrane protein β-catenin, which is translocated into the cell nucleus and regulates gene expression.