Aldosterone

Aldosterone
IUPAC name	a
Identifiers
CAS number	[52-39-1]
MeSH	Aldosterone
SMILES	OCC(=O)[C@H]4CC[C@@H]2[C@@]4 (C[C@H](O)[C@@H]1C3[C@H](C)CC (=O)/C=C3/CC[C@H]12)C=O
Properties
Molecular formula	C21H28O5
Molar mass	360,44 g/mol
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Aldosterone, is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland, and acts on the kidney nephron to conserve sodium, secrete potassium, and increase blood pressure. It is reduced in Addison\'s disease and increased in Conn syndrome.

It was first isolated by Simpson and Tait in 1953.Williams JS, Williams GH. 50th anniversary of aldosterone. J Clin Endocrinol Metab. 2003 Jun;88(6):2364-72. Full text. PMID 12788829.

Contents 1 Synthesis 1.1 Stimulation 2 Function 3 Location of receptors 4 Control of aldosterone release from the Adrenal Cortex 5 Additional images 6 See also 7 References

Synthesis

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).

Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). But aldosterone synthase is also able to perform a 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and reticularis.

Steroidogenesis, showing aldosterone synthesis at top.

Note: aldosterone synthase is absent in other sections of the adrenal gland.

Stimulation

Aldosterone synthesis is stimulated by several factors:

• by increased plasma angiotensin II, ACTH, or potassium levels, which are present in proportion to plasma sodium deficiencies. (The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in the zona glomerulosa, which opens the voltage-dependent calcium channels.) The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by the hormone renin. Potassium levels are the most sensitive stimulator of aldosterone.

• The ACTH stimulation test is sometimes use to stimulate the production of aldosterone along with cortisol to determine if primary or secondary adrenal insufficiency is present.

• by plasma acidosis.

• by the stretch receptors located in the atria of the heart. If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat and the gut. This causes increased osmolarity in the extracellular fluid which will eventually return blood pressure toward normal.

The secretion of aldosterone has a diurnal rhythm.Hurwitz S, Cohen R, & Williams GH. Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged bed rest. 2004 J Appl Physiol 96: 1406-1414. Full Text

Function

Aldosterone is the primary of several endogenous members of the class of mineralocorticoids in human. Deoxycorticosterone is another important member of this class. At the late distal tubule & collecting duct, aldosterone has two main actions:

1. Acting on mineralocorticoid receptors (MR) on principal cells in the collecting duct of the kidney nephron, it increases the permeability of their apical (luminal) membrane to potassium and sodium and activates their basolateral Na⁺/K⁺ pumps, stimulating ATP hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na⁺ ions to the outside. The phosphorylated form of the pump has a low affinity for Na⁺ ions, hence reabsorbing sodium (Na⁺) ions and water into the blood, and secreting potassium (K⁺) ions into the urine. (Chlorine anions are also reabsorbed in conjunction with sodium cations to maintain the system\'s electrochemical balance.)
2. Aldosterone stimulates H⁺ secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO₃⁻) levels and its acid/base balance.Brenner & Rector\'s The Kidney, 7th ed. Saunders, 2004.
3. Aldosterone may act on the central nervous system via the posterior pituitary gland to release vasopressin (ADH) which serves to conserve water by direct actions on renal tubular resorption.

Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal GFR (glomerular filtration rate).Sherwood, L. Human Physiology, from Cells to Systems, 4th Ed., Brooks/Cole, 2001

Aldosterone, most probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus. Fischer AK, von Rosenstiel P, Fuchs E, Goula D, Almeida OF, Czéh B, 2002 Aug

Location of receptors

Unlike neuroreceptors, classic steroid receptors are intracellularly located. The aldosterone/MR receptor complex binds on the DNA to specific hormone response element, which leads to gene specific transcription.

Some of the transcribed genes are crucial for transepithelial sodium transport, including the three subunits of the epithelial sodium channel, the Na⁺/K⁺ pumps and their regulatory proteins serum and glucocorticoid-induced kinase, and channel-inducing factor respectively.

Control of aldosterone release from the Adrenal Cortex

• The role of the renin-angiotensin system:

Angiotensin is involved in regulating aldosterone and is the core regulation. Williams GH Dluhy RG 1972 Am. J. Med. 53; 595. Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present. Pratt JH 1982 Angiotensin II in potassium mediated stimulation of aldosterone secretion in the dog. Journal of Clin. Invest. 70; 667. A small portion of the regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries. Messerli PT Wojciech N Masanobu H Genest J Boucher R Kuchel O Rojoortega JM 1977 Effects of angiotensin II on steroid metabolism and hepatic blood flow in man. Circulation Research 40; 204-207. When the blood flow decreases so does the destruction of aldosterone by liver enzymes.

• The role of sympathetic nerves:

The aldosterone production is also affected to one extent or another by nervous control which integrates the inverse of carotid artery pressure, Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610. pain, posture, Farrell G 1958 Regulation of aldosterone secretion. Phys. Rev. 38; 709. and probably emotion (anxiety, fear, and hostility) Venning EH Dyrenfurthen JC Beck J 1957 Effect of anxiety upon aldosterone excretion in man. J.Clinical Endocrinology and Metabolism. 17;10. (including surgical stress). Elman, R., et al. 1952 Intracellular and Extracellular Potassium Deficits in Surgical Patients. Ann. Surgery 136; 111. Anxiety increases aldosterone, Venning EH Dyrenfurthen JC Beck J 1957 Effect of anxiety upon aldosterone excretion in man. J.Clinical Endocrinology and Metabolism. 17;10. which must have evolved because of the time delay involved in migration of aldosterone into the cell nucleus. Sharp GUG Leaf A 1966 in; Recent Progress in Hormone Research.(Pincus G, ed. Thus, there is an advantage to an animal anticipating a future need from interaction with a predator since too high a serum content of potassium has very adverse effects on nervous transmission.

• The role of baroreceptors:

Pressure in the carotid artery decreases aldosterone Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610.*The role of the juxtaglomerular apparatus:

• The plasma concentration of potassium:

The amount of aldosterone secreted is a direct function of the serum potassium Bauer JH & Gauntner WC 1974 Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man. Kidney International 15; 286. Linas SL Peterson LN Anderson RJ Aisenbrey GA Simon FR Berl T 1979 Mechanism of renal potassium conservation in the rat. Kidney International 15; 601-611. as probably determined by sensors in the carotid artery. Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610. Gann DS Cruz JF Casper AGT Bartter FC 1962 Mechanism by which potassium increases aldosterone secretion in the dog. American Journal Phys. 202; 991.

• The plasma concentration of sodium:

Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure. Schneider EG Radke KJ Ulderich DA Taylor RE 1985 Effect of osmolality on aldosterone secretion. Endocrinology 116; 1621-1626. The slope of the response of aldosterone to serum potassium is almost independent of sodium intake. Dluhy RG Axelrod L Underwood RH & Williams GH 1972 Journal of Clinical Investigation 51; 1950. Aldosterone is much increased at low sodium intakes, but the rate of increase of plasma aldosterone as potassium rises in the serum is not much lower at high sodium intakes than it is at low. Thus, the potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in primitive diets.

• Miscellaneous regulation:

ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating DOC formation which is a precursor of aldosterone. Brown RD & Strott CA Liddle GW 1972 Site of stimulation of aldosterone biosynthesis by angiotensin and potassium. Journal of Clinical Investigation 51; 1413-1418. Aldosterone is increased by blood loss, Ruch TC Fulton JF 1960 Medical Physiology and Biophysics. W.B. Saunders and Co., Phijl & London. On p1099. pregnancy, Farrell G 1958 Regulation of aldosterone secretion. Phys. Rev. 38; 709. and possibly by other circumstances such as physical exertion, endotoxin shock, and burns. Glaz E & Vecsei P 1971 Aldosterone, Pergamon Press, NY

+Rauschkolb EW & Farrell GL 1956 Evidence for diencephatic regulation of aldosterone secretion. Endocrinology 59; 526-531, on o529.

• Aldosterone feedback:

Feedback by aldosterone concentration itself is of a non morphological character (that is other than changes in the cells\' number or structure) and is poor so the electrolyte feedbacks predominate short term. Glaz E & Vecsei P 1971 Aldosterone, Pergamon Press, NY

Additional images

Corticosteroid-biosynthetic-pathway-rat.png Corticosteroid biosynthetic pathway in rat

Steroidogenesis.gif Steroidogenesis

Corticosterone.svg Corticosterone

See also

• Aldosterone antagonist

References

v • d • e Endocrine system: hormones/endocrine glands (Peptide hormones, Steroid hormones)
Hypothalamic-pituitary	Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α (FSH, LH, TSH), GH, prolactin, POMC (ACTH, MSH, endorphins, lipotropin)
Adrenal axis	Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA
Thyroid axis	Thyroid: thyroid hormone (T3 and T4) - calcitonin - Parathyroid: PTH
Gonadal axis	Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin (pregnancy)
Other end. glands	Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin
Non-end. glands	Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Target-derived	NGF, BDNF, NT-3

v • d • e Urinary system, physiology: renal physiology and acid base physiology
Filtration	Renal blood flow - Ultrafiltration - Countercurrent exchange
Hormones affecting filtration	Antidiuretic hormone (ADH) - Aldosterone - Atrial natriuretic peptide
Secretion/clearance	Pharmacokinetics - Clearance of medications
Reabsorption	Solvent drag -Na+ - Cl- -urea -glucose -oligopeptides -protein
Endocrine	Renin - Erythropoietin (EPO) - Calcitriol (Active vitamin D) - Prostaglandins
Assessing Renal function / Measures of dialysis	Glomerular filtration rate - Creatinine clearance - Renal clearance ratio - Urea reduction ratio - Kt/V - Standardized Kt/V - Hemodialysis product - PAH clearance (Effective renal plasma flow - Extraction ratio)
Acid base physiology	Fluid balance - Darrow Yannet diagram - Body water - Interstitial fluid - Extracellular fluid - Intracellular fluid/Cytosol - Plasma - Transcellular fluid - Base excess - Davenport diagram - Anion gap - Arterial blood gas
Buffering/compensation	Bicarbonate buffering system - Respiratory compensation - Renal compensation

v • d • e Corticosteroids - glucocorticoid/receptor and mineralocorticoid/receptor (A07EA, C05AA, D07, D10AA, H02, R01AD, R03BA, S01BA, S02B, and S03B)
Endogenous	Aldosterone, Cortisone, Hydrocortisone/cortisol, Desoxycortone
Others	Alclometasone, Amcinonide, Beclometasone, Betamethasone, Budesonide, Ciclesonide, Clobetasol, Clobetasone, Clocortolone, Cloprednol, Cortivazol, Deflazacort, Deoxycorticosterone, Desonide, Desoximetasone, Dexamethasone, Diflorasone, Diflucortolone, Difluprednate, Fluclorolone, Fludrocortisone, Fludroxycortide, Flumetasone, Flunisolide, Fluocinolone acetonide, Fluocinonide, Fluocortin, Fluocortolone, Fluorometholone, Fluperolone, Fluprednidene, Fluticasone, Formocortal, Halcinonide, Halometasone, Hydrocortisone aceponate, Hydrocortisone buteprate, Hydrocortisone butyrate, Loteprednol, Medrysone, Meprednisone, Methylprednisolone,Methylprednisolone aceponate, Mometasone furoate, Paramethasone, Prednicarbate, Prednisone, Prednisolone, Prednylidene, Rimexolone, Tixocortol, Triamcinolone, Ulobetasol

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