Aldosterone 375130 224753105 2008-07-10T07:41:31Z Mac 7858 /* Stimulation */ {{Chembox new | ImageFile = Aldosterone.svg | ImageSize = | IUPACName = a | OtherNames = | Section1 = {{Chembox Identifiers | CASNo = 52-39-1 | PubChem = | SMILES = OCC(=O)[C@H]4CC[C@@H]2[C@@]4<br>(C[C@H](O)[C@@H]1C3[C@H](C)CC<br>(=O)/C=C3/CC[C@H]12)C=O | MeSHName = Aldosterone }} | Section2 = {{Chembox Properties | Formula = C<sub>21</sub>H<sub>28</sub>O<sub>5</sub> | MolarMass = 360,44 g/mol | Appearance = | Density = | MeltingPt = | BoilingPt = }} | Section3 = {{Chembox Hazards | Solubility = | MainHazards = | FlashPt = | Autoignition = }} }} '''Aldosterone''' is a hormone that causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body, and drives blood pressure up. Many drugs, such as [[spironolactone]], lower blood pressure by blocking the aldosterone receptor. Aldosterone is part of the [[renin-angiotensin-aldosterone system|renin-angiotensin system]]. 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 [[distal tubules]] and [[collecting ducts]] of the [[kidney]] to cause the conservation of [[sodium]], secretion of [[potassium]], increased water retention, and increased [[blood pressure]]. The overall effect of aldosterone is to increase reabsorption of ions and water in the kidney. Its activity is reduced in [[Addison's disease]] and increased in [[Conn syndrome]]. It was first isolated by Simpson and Tait in 1953.<ref>Williams JS, Williams GH. ''50th anniversary of aldosterone.'' J Clin Endocrinol Metab. 2003 Jun;88(6):2364-72. [http://jcem.endojournals.org/cgi/content/full/88/6/2364 Full text]. PMID 12788829.</ref> ==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 [[17&alpha;-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 [[11&beta;-hydroxylase]] (for [[corticosterone]]). These enzymes are nearly identical (they share 11&beta;-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]]; 11&beta;-hydroxylase is found in the [[zona fasciculata]] and [[reticularis]]. [[Image:Steroidogenesis.gif|thumb|right|400px|[[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 increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II. * by increased [[blood plasma|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 channel]]s.) 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 used 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 [[Atrium (heart)|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. * by adrenoglomerulotropin, a [[lipid factor]], obtained from pineal extracts. It selectively stimulates secretion of aldosterone <ref>http://circ.ahajournals.org/cgi/content/abstract/21/5/1009</ref>. The secretion of aldosterone has a [[Day|diurnal]] rhythm.<ref>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. [http://jap.physiology.org/cgi/content/full/96/4/1406 Full Text]</ref> ==Function== Aldosterone is the primary of several endogenous members of the class of [[mineralocorticoid]]s in human. [[Deoxycorticosterone]] is another important member of this class. At the late [[distal tubule]] & [[collecting duct]], aldosterone has three main actions: # Acting on the nuclear [[mineralocorticoid receptor]]s (MR) within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it increases the permeability of the [[Apical membrane|apical]] (luminal) membrane to potassium and sodium and activates the [[basolateral]] [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup> pumps]], stimulating [[Adenosine triphosphate|ATP]] hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na<sup>+</sup> ions to the outside. The phosphorylated form of the pump has a low affinity for Na<sup>+</sup> ions, hence reabsorbing sodium (Na<sup>+</sup>) ions and water into the blood, and secreting potassium (K<sup>+</sup>) ions into the urine. (Chlorine anions are also reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.) # Aldosterone stimulates H<sup>+</sup> secretion by [[intercalated cells]] in the collecting duct, regulating plasma [[bicarbonate]] (HCO<sub>3</sub><sup>−</sup>) levels and its acid/base balance.<ref>Brenner & Rector's The Kidney, 7th ed. Saunders, 2004.</ref> # 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. (reference needed) 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]]).<ref>Sherwood, L. Human Physiology, from Cells to Systems, 4th Ed., Brooks/Cole, 2001</ref> Aldosterone, most probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus. <ref>Fischer AK, von Rosenstiel P, Fuchs E, Goula D, Almeida OF, Czéh B, 2002 Aug </ref> ==Location of receptors== Unlike [[neuroreceptor]]s, 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 (genetics)|transcription]]. Some of the transcribed genes are crucial for [[transepithelial sodium transport]], including the three [[subunit]]s of the [[epithelial sodium channel]], the [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup> 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.<ref> Williams GH Dluhy RG 1972 Am. J. Med. 53; 595.</ref> Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present.<ref> Pratt JH 1982 Angiotensin II in potassium mediated stimulation of aldosterone secretion in the dog. Journal of Clin. Invest. 70; 667.</ref> 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.<ref> 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.</ref> 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,<ref> Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610.</ref> pain, posture,<ref> Farrell G 1958 Regulation of aldosterone secretion. Phys. Rev. 38; 709.</ref> and probably emotion (anxiety, fear, and hostility) <ref> Venning EH Dyrenfurthen JC Beck J 1957 Effect of anxiety upon aldosterone excretion in man. J.Clinical Endocrinology and Metabolism. 17;10.</ref> (including surgical stress).<ref> Elman, R., et al. 1952 Intracellular and Extracellular Potassium Deficits in Surgical Patients. Ann. Surgery</cite> 136; 111.</ref> Anxiety increases aldosterone,<ref> Venning EH Dyrenfurthen JC Beck J 1957 Effect of anxiety upon aldosterone excretion in man. J.Clinical Endocrinology and Metabolism. 17;10.</ref> which must have evolved because of the time delay involved in migration of aldosterone into the cell nucleus.<ref> Sharp GUG Leaf A 1966 in; Recent Progress in Hormone Research.(Pincus G, ed.</ref> 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 [[baroreceptor]]s: Pressure in the carotid artery decreases aldosterone <ref> Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610.</ref> *The role of the [[juxtaglomerular apparatus]]: *The plasma concentration of [[potassium]]: The amount of aldosterone secreted is a direct function of the serum potassium <ref> Bauer JH & Gauntner WC 1979 Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man. Kidney International 15; 286.</ref> <ref> 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.</ref> as probably determined by sensors in the carotid artery.<ref> Gann DS Mills IH Bartter 1960 On the hemodynamic parameter mediating increase in aldosterone secretion in the dog. Fed. Proceedings 19; 605-610.</ref><ref> Gann DS Cruz JF Casper AGT Bartter FC 1962 Mechanism by which potassium increases aldosterone secretion in the dog. American Journal Phys. 202; 991.</ref> *The plasma concentration of [[sodium]]: Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure.<ref> Schneider EG Radke KJ Ulderich DA Taylor RE 1985 Effect of osmolality on aldosterone secretion. Endocrinology 116; 1621-1626.</ref> The slope of the response of aldosterone to serum potassium is almost independent of sodium intake.<ref> Dluhy RG Axelrod L Underwood RH & Williams GH 1972 Journal of Clinical Investigation 51; 1950.</ref> 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.<ref> Brown RD & Strott CA Liddle GW 1972 Site of stimulation of aldosterone biosynthesis by angiotensin and potassium. Journal of Clinical Investigation 51; 1413-1418.</ref> Aldosterone is increased by blood loss,<ref> Ruch TC Fulton JF 1960 Medical Physiology and Biophysics. W.B. Saunders and Co., Phijl & London. On p1099.</ref> pregnancy,<ref> Farrell G 1958 Regulation of aldosterone secretion. Phys. Rev. 38; 709.</ref> and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.<ref> Glaz E & Vecsei P 1971 Aldosterone, Pergamon Press, NY<p>+Rauschkolb EW & Farrell GL 1956 Evidence for diencephatic regulation of aldosterone secretion. Endocrinology 59; 526-531, on o529.</ref> *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.<ref> Glaz E & Vecsei P 1971 Aldosterone, Pergamon Press, NY</ref> ==Additional images== <gallery> Image:Corticosteroid-biosynthetic-pathway-rat.png|Corticosteroid biosynthetic pathway in rat Image:Steroidogenesis.gif|[[Steroidogenesis]] Image:Corticosterone.svg|[[Corticosterone]] </gallery> ==See also== * [[Aldosterone antagonist]] * [[ACTH stimulation test]] ==References== {{Reflist|2}} {{Hormones}} {{Renal physiology}} {{Corticosteroids}} [[Category:Mineralocorticoids]] [[Category:Steroid hormones]] [[bg:Алдостерон]] [[cs:Aldosteron]] [[da:Aldosteron]] [[de:Aldosteron]] [[es:Aldosterona]] [[fr:Aldostérone]] [[it:Aldosterone]] [[lt:Aldosteronas]] [[hu:Aldoszteron]] [[nl:Aldosteron]] [[ja:アルドステロン]] [[no:Aldosteron]] [[oc:Aldosterona]] [[pl:Aldosteron]] [[pt:Aldosterona]] [[sk:Aldosterón]] [[fi:Aldosteroni]] [[sv:Aldosteron]] [[tr:Aldosteron]]