|
m |
| Line 1: |
Line 1: |
| - | '''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]].
| + | <table align='right' border=1> |
| | + | <tr><td> |
| | + | <jmol><jmolApplet> |
| | + | <size>200</size> |
| | + | <script>spin on;color atoms amino;</script> |
| | + | <uploadedFileContents>NPH110.SDF</uploadedFileContents> |
| | + | <color>black</color> |
| | + | </jmolApplet> |
| | + | </jmol> |
| | + | </td></tr></table> |
| | + | ==Description== |
| | + | A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. |
| | + | ==General Properties== |
| | | | |
| - | It was first isolated by Simpson and Tait in 1953.<ref>{{cite journal |author=Williams JS, Williams GH |title=50th anniversary of aldosterone |journal=J Clin Endocrinol Metab. |volume=88 |issue=6 |pages=2364–72 |year=2003 |month=Jun |pmid=12788829 |doi= 10.1210/jc.2003-030490|url=http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=12788829}}</ref>
| + | <b>*Molecular Weight</b> |
| | | | |
| - | Pubchem(5839)
| + | 360.44 |
| | | | |
| - | A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
| + | <b>*Molecular Formula</b> |
| | | | |
| - | '''KEGG Pathway'''(C01780)
| + | C<sub>2</sub><sub>1</sub>H<sub>2</sub><sub>8</sub>O<sub>5</sub> |
| - | *C21-Steroid hormone metabolism
| + | |
| - | {| border="1;width:100%; height:200px;style=text-align:center"
| + | |
| - | |+'''Physiochemical properties of Estriol:'''
| + | |
| - | |-
| + | |
| - | ! style="background:brown; color:white" |Physical Property
| + | |
| - | ! style="background:brown; color:white" |Value
| + | |
| - | ! style="background:brown; color:white" |Units
| + | |
| - | ! style="background:brown; color:white" |Temp (deg C)
| + | |
| - | ! style="background:brown; color:white" |Source
| + | |
| - | |-
| + | |
| - | |Melting Point
| + | |
| - | |166.5
| + | |
| - | |deg C
| + | |
| - | |
| + | |
| - | |EXP
| + | |
| - | |-
| + | |
| - | |log P (octanol-water)
| + | |
| - | |1.08
| + | |
| - | |(none)
| + | |
| - | |
| + | |
| - | |EXP
| + | |
| - | |-
| + | |
| - | |Water Solubility
| + | |
| - | |51.2
| + | |
| - | |mg/L
| + | |
| - | |37
| + | |
| - | |EXP
| + | |
| - | |-
| + | |
| - | |Vapor Pressure
| + | |
| - | |1.25E-12
| + | |
| - | |mm Hg
| + | |
| - | |25
| + | |
| - | |EST
| + | |
| - | |-
| + | |
| - | |Henry's Law Constant
| + | |
| - | |1.81E-13
| + | |
| - | |atm-m3/mole
| + | |
| - | |25
| + | |
| - | |EST
| + | |
| - | |-
| + | |
| - | |Atmospheric OH Rate Constant
| + | |
| - | |1.49E-10
| + | |
| - | |cm3/molecule-sec
| + | |
| - | |25
| + | |
| - | |EST
| + | |
| - | |-
| + | |
| - | |}
| + | |
| - | ==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]].
| + | <b>*IUPAC NAME</b> |
| | | | |
| - | [[Image:Steroidogenesis.svg|thumb|right|400px|[[Steroidogenesis]], showing aldosterone synthesis at bottom right corner.]]
| + | (8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde |
| | | | |
| - | Note: [[aldosterone synthase]] is absent in other sections of the [[adrenal gland]].
| + | <b>*Canonical Smiles</b> |
| - | ===Stimulation===
| + | |
| - | Aldosterone synthesis is stimulated by several factors:
| + | |
| | | | |
| - | * by increase in the plasma concentration of Angiotensin III, a metabolite of Angiotensin II.
| + | CC12CCC(=O)C=C1CCC3C2C(CC4(C3CCC4C(=O)CO)C=O)O |
| | | | |
| - | * 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. | + | <b>*Isomeric Smiles</b> |
| | | | |
| - | * 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.
| + | C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2[C@H](C[C@]4([C@H]3CC[C@@H]4C(=O)CO)C=O)O |
| | | | |
| - | * 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.
| + | ==PhysioChemical Properties== |
| | | | |
| - | * by adrenoglomerulotropin, a [[lipid factor]], obtained from pineal extracts. It selectively stimulates secretion of aldosterone <ref>{{cite journal |author=Farrell G |title=Adrenoglomerulotropin |journal=Circulation |volume=21 |issue= |pages=1009–15 |year=1960 |month=May |pmid=13821632 |doi= |url=http://circ.ahajournals.org/cgi/content/abstract/21/5/1009}}</ref>.
| + | <b>*Melting Point</b> |
| | | | |
| - | The secretion of aldosterone has a [[Day|diurnal]] rhythm.<ref>{{cite journal |author=Hurwitz S, Cohen RJ, Williams GH |title=Diurnal variation of aldosterone and plasma renin activity: timing relation to melatonin and cortisol and consistency after prolonged [[bed rest]] |journal=J App Physiol |volume=96 |issue=4 |pages=1406–14 |year=2004 |month=Apr |pmid=14660513 |doi=10.1152/japplphysiol.00611.2003 |url=http://jap.physiology.org/cgi/content/full/96/4/1406}}</ref>
| + | 166.5(EXP) |
| - | ==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.)
| + | <b>*LogP</b> |
| - | # 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>{{cite book |author=Rector, Floyd C.; Brenner, Barry M. |title=Brenner & Rector's the kidney |publisher=Saunders |location=Philadelphia |year=2004 |pages= |isbn=0-7216-0164-2 |oclc= 51838812|doi= |accessdate=}}</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>{{cite book |author=Sherwood, Lauralee |title=Human physiology: from cells to systems |publisher=Brooks/Cole |location=Pacific Grove, CA |year=2001 |pages= |isbn=0-534-56826-2 |oclc= 43702042|doi= |accessdate=}}</ref>
| + | 1.08(EXP) |
| | | | |
| - | Aldosterone, most probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the dentate gyrus. <ref>{{cite journal |author=Fischer AK, von Rosenstiel P, Fuchs E, Goula D, Almeida OF, Czéh B |title=The prototypic mineralocorticoid receptor agonist aldosterone influences neurogenesis in the dentate gyrus of the adrenalectomized rat |journal=Brain Res. |volume=947 |issue=2 |pages=290–3 |year=2002 |month=Aug |pmid=12176172 |doi= 10.1016/S0006-8993(02)03042-1|url=http://linkinghub.elsevier.com/retrieve/pii/S0006899302030421}}</ref>
| + | <b>*Water Solubility</b> |
| | | | |
| - | ==Location of receptors==
| + | 51.2(EXP) at 37C |
| - | 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.
| + | ==External Links== |
| | + | *[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5839]Pubchem |
| | + | *[http://www.genome.jp/dbget-bin/www_bget?compound+C01780]]KEGG Compound |
| | + | *[http://www.hmdb.ca/metabolites/HMDB00037]Human Metabolome DataBase |
| | + | *[http://www.drugbank.ca/drugs/DB04630]Drugbank |
| | | | |
| - | ==Control of aldosterone release from the Adrenal Cortex==
| + | [[Categories:Hormones]] |
| - | *The role of the [[renin-angiotensin system]]:
| + | |
| - | Angiotensin is involved in regulating aldosterone and is the core regulation.<ref>{{cite journal |author=Williams GH, Dluhy RG |title=Aldosterone biosynthesis. Interrelationship of regulatory factors |journal=Am J Med |volume=53 |issue=5 |pages=595–605 |year=1972 |month=Nov |pmid=4342886 |doi= 10.1016/0002-9343(72)90156-8|url=http://linkinghub.elsevier.com/retrieve/pii/0002-9343(72)90156-8}}</ref> Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present.<ref>{{cite journal |author=Pratt JH |title=Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog |journal=J Clin Invest. |volume=70 |issue=3 |pages=667–72 |year=1982 |month=Sep |pmid=6286729 |pmc=370270 |doi= 10.1172/JCI110661|url=}}</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>{{cite journal |author=Messerli FH, Nowaczynski W, Honda M, ''et al'' |title=Effects of angiotensin II on steroid metabolism and hepatic blood flow in man |journal=Circulation Research |volume=40 |issue=2 |pages=204–7 |year=1977 |month=Feb |pmid=844145 |doi= |url=}}</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 name=autogenerated2> 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 name=autogenerated1>{{cite journal |author=Farrell G |title=Regulation of aldosterone secretion |journal=Physiological Reviews |volume=38 |issue=4 |pages=709–28 |year=1958 |month=Oct |pmid=13590935 |doi= |url=http://physrev.physiology.org/cgi/pmidlookup?view=long&pmid=13590935}}</ref> and probably emotion (anxiety, fear, and hostility) <ref name=autogenerated3>{{cite journal |author=Venning EH, DyrenfurthY I, Beck JC |title=Effect of anxiety upon aldosterone excretion in man |journal=J Clin Endocrinol Metab. |volume=17 |issue=8 |pages=1005–8 |year=1957 |month=Aug |pmid=13449153 |doi= |url=}}</ref> (including surgical stress).<ref>{{cite journal |author=Elman R, Shatz BA, Keating RE, Weichselbaum TE |title=Intracellular and extracellular potassium deficits in surgical patients |journal=Annals of surgery |volume=136 |issue=1 |pages=111–31 |year=1952 |month=Jul |pmid=14934025 |pmc=1802239 |doi= 10.1097/00000658-195208000-00013|url=}}</ref> Anxiety increases aldosterone,<ref name=autogenerated3 /> 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 name=autogenerated2 />
| + | |
| - | *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>{{cite journal |author=Bauer JH, Gauntner WC |title=Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man |journal=Kidney Int. |volume=15 |issue=3 |pages=286–93 |year=1979 |month=Mar |pmid=513492 |doi= 10.1038/ki.1979.37|url=}}</ref><ref>{{cite journal |author=Linas SL, Peterson LN, Anderson RJ, Aisenbrey GA, Simon FR, Berl T |title=Mechanism of renal potassium conservation in the rat |journal=Kidney Int. |volume=15 |issue=6 |pages=601–11 |year=1979 |month=Jun |pmid=222934 |doi= 10.1038/ki.1979.79|url=}}</ref> as probably determined by sensors in the carotid artery.<ref name=autogenerated2 /><ref>{{cite journal |author=Gann DS, Cruz JF, Casper AG, Bartter FC |title=Mechanism by which potassium increases aldosterone secretion in the dog |journal=Am J Physiol. |volume=202 |issue= |pages=991–6 |year=1962 |month=May |pmid=13896654 |doi= |url=http://ajplegacy.physiology.org/cgi/pmidlookup?view=long&pmid=13896654}}</ref>
| + | |
| - | *The plasma concentration of [[sodium]]:
| + | |
| - | Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure.<ref>{{cite journal |author=Schneider EG, Radke KJ, Ulderich DA, Taylor RE |title=Effect of osmolality on aldosterone secretion |journal=Endocrinology |volume=116 |issue=4 |pages=1621–6 |year=1985 |month=Apr |pmid=3971930 |doi= |url=}}</ref> The slope of the response of aldosterone to serum potassium is almost independent of sodium intake.<ref>{{cite journal |author=Dluhy RG, Axelrod L, Underwood RH, Williams GH |title=Studies of the control of plasma aldosterone concentration in normal man. II. Effect of dietary potassium and acute potassium infusion |journal=J Clin Invest. |volume=51 |issue=8 |pages=1950–7 |year=1972 |month=Aug |pmid=5054456 |pmc=292351 |doi=10.1172/JCI107001 |url=}}</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>{{cite journal |author=Brown RD, Strott CA, Liddle GW |title=Site of stimulation of aldosterone biosynthesis by angiotensin and potassium |journal=J Clin Invest. |volume=51 |issue=6 |pages=1413–8 |year=1972 |month=Jun |pmid=4336939 |pmc=292278 |doi=10.1172/JCI106937 |url=}}</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 name=autogenerated1 /> and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.<ref name=Glaz>{{cite book |author=Vecsei, Pál; Gláz, Edith |title=Aldosterone |publisher=Pergamon Press |location=New York |year=1971 |pages= |isbn=0-08-013368-1 |oclc= 186705|doi= |accessdate=}}</ref><ref>{{cite journal |author=Farrell GL, Rauschkolb EW |title=Evidence for diencephalic regulation of aldosterone secretion |journal=Endocrinology |volume=59 |issue=5 |pages=526–31 |year=1956 |month=Nov |pmid=13375573 |doi= |url=}} on 529</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 name=Glaz/>
| + | |
| - | | + | |
| - | ==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]]
| + | |
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
(8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde
