Trends in Endocrinology & Metabolism
Aldosterone Secretion: A Molecular Perspective
Section snippets
• Regulation of Aldosterone Biosynthesis
Since the isolation of aldosterone by Simpson et al. (1954), much has been learned about its biosynthesis, regulation of biosynthesis, modes of actions, and metabolism. The further characterization of aldosterone regulation, particularly of the mechanisms turning off aldosterone secretion, may produce clues to the etiology of hypertensive syndromes that are characterized by over-production of this important mineralocorticoid hormone.
During these past 4 decades, it has become widely accepted
• Aldosterone Biosynthesis
Aldosterone is synthesized from cholesterol, as are the other adrenal steroids. The transport of cholesterol from the outer to the inner mitochondrial membrane is the rate-limiting step in steroidogenesis (Jefcoate et al. 1987). Recently, the carrier protein responsible for this transport has been identified (King et al. 1995). This protein is referred to as the steroidogenic acute regulatory (StAR) protein and is associated exclusively with the mitochondria [refer to review by Stocco and Clark
• Clinical Studies
Characterization of diseases caused by inherited defects in cortisol and aldosterone biosynthesis confirmed the hypothesis that in the human, P45011β is required for normal cortisol synthesis and P450aldo is required for aldosterone synthesis.
Glucocorticoid- (or Dexamethasone-) Remediable Aldosteronism
Glucocorticoid-remediable aldosteronism (GRA), also known as familial hyperaldosteronism type I (FH I), glucocorticoid-suppressible hyperaldosteronism (GSH), or dexamethasone-suppressible hyperaldosteronism (DSH), is a rare disorder that is characterized by moderate hypersecretion of aldosterone, suppressed plasma renin activity (PRA), and rapid correction of these abnormalities after administration of the glucocorticoid dexamethasone. It is a disease showing autosomal dominant inheritance.
In
Acknowledgements
The authors thank Professors J.F. Tait and S.A. Tait for their helpful comments. K.M. Curnow is the recipient of a Fellowship from the Australian Foundation for High Blood Pressure Research. This work has been funded by a block grant to the Howard Florey Institute from NH&MRC of Australia.
References (89)
- et al.
Demonstration of an angiotensin II-induced negative feedback effect on aldosterone synthesis in isolated rat adrenal zona glomerulosa cells
Mol Cell Endocrinol
(1996) - et al.
Circulating angiotensin-II and aldosterone levels during dietary sodium restriction
Lancet
(1971) - et al.
Cloning and expression analysis of a cytochrome P-45011β cDNA in sheep
Biochem Biophys Acta
(1995) - et al.
Raised plasma angiotensin II and aldosterone during dietary sodium restriction in man
Lancet
(1972) - et al.
The steroidogenic acute regulatory protein is induced by angiotensin II and K+ in H295R adrenocortical cells
Mol Cell Endocrinol
(1995) - et al.
ACTH regulation of cholesterol movement in isolated adrenal cells
J Steroid Biochem
(1987) - et al.
Cloning of cDNA and genomic DNA for human P-450(11β)
FEBS Lett
(1990) - et al.
Purification and characterization of two distinct forms of rat adrenal cytochrome P-45011β: functional and structural aspects
Arch Biochem Biophys
(1989) - et al.
Adrenocortical pregnenolone-binding protein: identification and antibody development
Biochem Biophys Res Commun
(1988) - et al.
The presence of two cytochrome P-450 aldosterone synthase mRNAs in hamster adrenal
J Steroid Biochem Mol Biol
(1994)
Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients
Biochem Biophys Res Commun
Characterization of two genes encoding human steroid 11β-hydroxylase (P-45011β)
J Biol Chem
CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450c18)
Biochem Biophys Res Commun
Functional expression of cDNAs for bovine 11β-hydroxylase-aldosterone synthases, 450(11β)-2 and -3 and their chimeras
J Steroid Biochem Mol Biol
Genetic recombination as a cause of inherited disorders of aldosterone and cortisol biosynthesis and a contributor to genetic variation in blood pressure
Steroids
Pathogenesis of mineralocorticoid hypertension
Clin Endocrinol Metab
The role of the steroidogenic acute regulatory protein in steroidogenesis
Steroids
Cloning and expression of cytochrome P450(11β) of porcine adrenal cortex
J Steroid Biochem Mol Biol
Expression of inositol 1,4,5-triphosphate receptors in rat adrenocortical zones
J Steroid Biochem Mol Biol
The effect of changes in potassium concentration on the maximal steroidogenic response of purified zona glomerulosa cells to angiotensin II
J Steroid Biochem
The hamster adrenal cytochrome P450C11 has equipotent 11β-hydroxylase and 19-hydroxylase activities, but no aldosterone synthase activity
J Steroid Biochem Mol Biol
The biosynthesis of aldosterone
J Steroid Biochem Mol Biol
Angiotensin II-induced inositol phosphate production in isolated rat zona glomerulosa and fasciculata/reticularis cells
Steroids
Classic steroid 11β-hydroxylase deficiency caused by a C→G transversion in exon 7 of CYP11B1
Biochem Biophys Res Commun
The hybrid rat cytochrome P450 containing the first 5 exons of the CYP11B1 and last 4 exons from the CYP11B2 enzyme retains 11β-hydroxylase activity, but the alternative hybrid is inactive
Biochem Biophys Res Commun
The in vitro demonstration of differential corticosteroid production within the ox adrenal gland
Biochem J
Humoral stimulation of adrenocortical secretion
J Clin Invest
Effect of change of sodium balance on the corticosteroid response to angiotensin II
Aust J Exp Biol Med Sci
The dissociation of aldosterone secretion and systemic renin and angiotensin II levels during the correction of sodium deficiency
Acta Endocrinol (Copenh)
Inhibition of renin secretion by systemic and intrarenal angiotensin infusion
Am J Physiol
Perspectives in aldosterone and renin control
Aust N Z J Med
The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex
Mol Endocrinol
Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8
Proc Natl Acad Sci USA
The amino acid substitutions Ser 288Gly and Val320Ala convert the cortisol producing enzyme, CYP11B1, into an aldosterone producing enzyme
Nat Struct Biol
The renin-angiotensin system in the control of aldosterone secretion in the rat
Acta Physiol Lat Am
Morphological and histochemical study of rat's adrenal cortex after hypophysectomy, with comments on liver
Am J Anat
Different isozymes of mouse 11β-hydroxylase produce mineralocorticoids and glucocorticoids
Mol Endocrinol
Gene conversion in the CYP11B2 gene encoding P450c11AS is associated with, but does not cause, the syndrome of corticosterone methyl oxidase II deficiency
J Clin Endocrinol Metab
Role of calcium and other mediators in aldosterone secretion from the adrenal glomerulosa cells
Pharmacol Rev
Amino acid substitution R384P in aldosterone synthase causes corticosterone methyl oxidase type I deficiency
J Clin Endocrinol Metab
CYP11B1 mutations causing congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
J Clin Endocrinol Metab
Cited by (18)
A case of primary selective hypoaldosteronism carrying three mutations in the aldosterone synthase (Cyp11b2) gene
2012, GeneCitation Excerpt :The 11β-hydroxylation, 18-hydroxylation, and 18-oxidation activities are mediated by the heme group contained in the core of enzyme active site. The aldosterone synthase is expressed exclusively in the cells of the adrenal zona glomerulosa, effectively limiting the synthesis of aldosterone to that zone (Boon et al., 1997; White, 2004). The function of the similar cytochrome P450 enzyme (CYP11B1, P450c11β) encoded by the Cyp11b1 gene is inefficient to convert the B to 18OHB substrate (White, 2004).
Protein kinase Cμ mediates adenosine-stimulated steroidogenesis in primary rat adrenal cells
2010, FEBS LettersCitation Excerpt :Corticosterone production requires the translation of cytochrome P450 hydrolase (CYP11A1, CYP17, CYP21, CYP11B1), hormone sensitive lipase, and StAR [23]. Among them, 11β-hydroxylase, encoded by CYP11B1 gene, catalyzes the production of corticosterone [24]. Ado induced mRNA expression of CYP11B1, and this effect was abolished by PKC inhibition (calphostin C pretreatment) (Fig. 3B).
Adrenal minerlocorticoids pathway and its clinical applications
2003, Clinica Chimica ActaAldosterone secretion by the mid-gestation ovine fetus: Role of the AT<inf>2</inf> receptor
1999, Molecular and Cellular EndocrinologyOntogeny and regulation of the AT<inf>1</inf> and AT<inf>2</inf> receptors in the ovine fetal adrenal gland
1999, Molecular and Cellular EndocrinologyAngiotensin and aldosterone
1999, Regulatory Peptides