cGMP‐dependent protein kinase II and aldosterone secretion

Abstract

ACTH‐stimulated aldosterone secretion can be inhibited by atrio‐natriuretic peptide/cGMP. The mechanism behind this modulation has been reported to involve cGMP‐dependent activation of phosphodiesterase 2 (PDE2) and hydrolysis of cAMP. Recently it was reported that activation of cGMP‐dependent protein kinase II (cGKII) stimulated aldosterone secretion in rat zona glomerulosa cells. The zona glomerulosa of the murine adrenal cortex expresses cGKII and PDE2. We used mice with a homozygous inactivation of the cGKII gene to investigate in vivo the potential role of this kinase in aldosterone secretion. Basal plasma renin and aldosterone levels were similar in wild‐type and cGKII−/− mice. In vivo injection of atrio‐natriuretic peptide decreased ACTH‐stimulated aldosterone secretion in wild‐type mice, but had no effect in cGKII‐deficient mice. These results support the view that cGKII modulates aldosterone secretion in the murine adrenal cortex.

Alterations of Phosphodiesterases in Adrenocortical Tumors

“…Three PDE2A isoforms exist: PDE2A1, PDE2A2, and PDE2A3, and exhibit higher affinity for cGMP than cAMP (33). PDE2A is implicated in the downregulation of aldosterone production in adrenal zona glomerulosa cells and the regulation of the ACTH-induced increase in intracellular cAMP (11). This ACTH response is described as a rapid and sustained activation of AC followed by a biphasic effect of ACTH on PDE2 activity with an initial and rapid inhibition, followed by a delayed activation (11).…”

“…PDE2A is implicated in the downregulation of aldosterone production in adrenal zona glomerulosa cells and the regulation of the ACTH-induced increase in intracellular cAMP (11). This ACTH response is described as a rapid and sustained activation of AC followed by a biphasic effect of ACTH on PDE2 activity with an initial and rapid inhibition, followed by a delayed activation (11). In one study, PDE2 involvement was observed to be more important in rat than in human adrenal glomerulosa cells, whereas AC was more stimulated in human than in rat glomerulosa cells (34).…”

“…PDEs vary in a number of ways, including a difference in substrate selectivity, tissue distribution, kinetic, and tissue expression (Table 1). The adrenal cortex expresses several isoforms of PDEs, including PDE2A that has been implicated in the downregulation of aldosterone production in adrenal zona glomerulosa cells and the regulation of the adrenocorticotropic hormone (ACTH)-induced increase in intracellular cAMP in the zona fasciculata cells (11). …”

The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis

“…More recently, the ANP-stimulated PDE2A decrease in cAMP has been confirmed by real-time imaging in bovine glomerulosa cells [20]. Surprisingly, the inhibitory effect of ANP on ACTH-stimulated aldosterone production is slightly blunted in PKGII −/− animals compared to WT [21]. However, it remains unclear if PKGII directly modulates this inhibitory effect on aldosterone production.…”

Common Variants of cGKII/PRKG2 Are Not Associated with Gout Susceptibility

“…The most established function of cGKII is the regulation of renin and aldosterone secretion 13,19 . Thus, dysfunction of the cGKII gene could cause hypertension through the renin-angiotensin-aldosterone system.…”