Acute and chronic regulation of aldosterone production

Abstract

Aldosterone is the major mineralocorticoid synthesized by the adrenal. Secretion of aldosterone is regulated tightly by the adrenocortical glomerulosa cells due to the selective expression of CYP11B2 in the outermost zone, the zona glomerulosa. Aldosterone is largely responsible for regulation of systemic blood pressure through the absorption of electrolytes and water under the regulation of certain specific agonists. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main physiological agonists which regulate aldosterone secretion. The mechanisms involved in this process may be regulated minutes after a stimulus (acutely) through increased expression and phosphorylation of the steroidogenic acute regulatory (StAR) protein, over hours to days (chronically) by increased expression of the enzymes involved in the synthesis of aldosterone, particularly aldosterone synthase (CYP11B2). Imbalance in any of these processes may lead to several aldosterone excess disorders. In this review we attempt to summarize the key molecular events involved in and specifically attributed to the acute and chronic phases of aldosterone secretion.

Cholesteryl Ester-Transfer Protein Inhibitors Stimulate Aldosterone Biosynthesis in Adipocytes through Nox-Dependent Processes

“…StAR, which is regulated by CREB, plays an important role in the acute generation of aldosterone through processes dependent on cholesterol flux into the mitochondria and conversion to pregnenolone. Aldosterone is also controlled chronically by CYP11B2 (Hattangady et al, 2012). Our results show differential regulation of these enzymes by CETP inhibitors.…”

“…We studied human and mouse adipocytes and found similar responses in both cell types, indicating that CETP inhibitor-induced adipocyte aldosterone production is independent of CETP, since mice lack the CETP gene. The biosynthesis of aldosterone has been very well characterized in adrenal cells and is mediated by StAR and the rate-limiting enzyme CYP11B2 (Hattangady et al, 2012). Both enzymes are expressed in adipocytes and the three CETP inhibitors studied here significantly increased their expression.…”

“…StAR transports cholesterol into the mitochondria and plays an important role in aldosterone production (Hattangady et al, 2012). Expression of StAR at the mRNA and protein levels, was increased by CETP inhibitors ( Fig.…”

Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion

“…Under acute stimulatory conditions the site of action is, in both cases, the Steroidogenic Acute Regulatory Protein (StAR) that facilitates the cholesterol transport to the cholesterol side chain cleaving enzyme (cytochrome P450 scc ), located on the inner mitochondrial membrane (reviewed in (Hattangady et al, 2011;Spät and Hunyady, 2004)). Calcium ions exert intramitochondrial action(s) as well.…”

Extramitochondrial OPA1 and adrenocortical function

“…We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial (Hattangady et al, 2011;Vinson et al, 1992). Deesterification is 57 performed again by HSL (Kraemer et al, 2004).…”