Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Aldosterone: Difference between pages

{{Short description|Mineralocorticoid steroid hormone}}

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{{Chembox

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| ImageCaption = [[Skeletal formula]] of the fictitious aldehyde form<ref>{{ cite journal | title = Absolute content determination by quantitative NMR (qNMR) spectroscopy: a curious case of aldosterone | first1 = Neeraj | last1 = Singh | first2 = Judith | last2 = Taibon | first3 = Stephan | last3 = Pongratz | first4 = Christian | last4 = Geletneky | journal = [[RSC Advances|RSC Adv.]] | year = 2021 | volume = 11 | issue = 38 | pages = 23627–23630 | doi = 10.1039/D1RA03472C | pmid = 35479823 | pmc = 9036601 | bibcode = 2021RSCAd..1123627S }}</ref>

| ImageFile1 = Aldosterone-18-acetal-20-hemiketal-from-xtal-3D-bs-17.png

| ImageCaption1 = [[Ball-and-stick model]] of the 18-acetal-20-hemiketal form based on [[crystallography]]<ref name="ALDAHA10">{{ cite journal | url = https://www.ccdc.cam.ac.uk/structures/Search?Ccdcid=1102212&DatabaseToSearch=Published | title = CSD Entry: ALDAHA10 | website = [[Cambridge Structural Database]]: Access Structures | year = 1972 | publisher = [[Cambridge Crystallographic Data Centre]] | access-date = 2022-09-03 }}</ref><ref>{{ cite journal | first1 = William L. | last1 = Duax | first2 = Herbert | last2 = Hauptman | title = Crystal structure and molecular conformation of aldosterone | journal = [[Journal of the American Chemical Society|J. Am. Chem. Soc.]] | year = 1972 | volume = 94 | issue = 15 | pages = 5467–5471 | doi = 10.1021/ja00770a050 | pmid = 5040851 }}</ref>

| SystematicName = (1''S'',3a''S'',3b''S'',9a''R'',9b''S'',10''S'',11a''R'')-10-Hydroxy-1-(hydroxyacetyl)-9a-methyl-7-oxo-1,2,3,3a,3b,4,5,7,8,9,9a,9b,10,11-tetradecahydro-11a''H''-cyclopenta[''a'']phenanthrene-11a-carbaldehyde

| OtherNames = Aldocorten; Aldocortin; Electrocortin; Reichstein X; 18-Aldocorticosterone; 18-Oxocorticosterone

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 2872

| InChI = 1/C21H28O5/c1-20-7-6-13(24)8-12(20)2-3-14-15-4-5-16(18(26)10-22)21(15,11-23)9-17(25)19(14)20/h8,11,14-17,19,22,25H,2-7,9-10H2,1H3/t14-,15-,16+,17-,19+,20-,21+/m0/s1

| InChIKey = PQSUYGKTWSAVDQ-ZVIOFETBBV

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

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| PubChem = 5839

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| ChEBI_Ref = {{ebicite|correct|EBI}}

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| MeSHName = Aldosterone

| UNII_Ref = <!--{{fdacite|changed|FDA}}-->{{fdacite|correct|FDA}}

| UNII = 4964P6T9RB

| KEGG = D10528

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|Section6={{Chembox Pharmacology

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'''Aldosterone''' is the main mineralocorticoid [[steroid hormone]] produced by the [[zona glomerulosa]] of the [[adrenal cortex]] in the [[adrenal gland]].<ref>{{cite journal|date=January 2016|title=Emerging Roles of the Mineralocorticoid Receptor in Pathology|journal=[[Pharmacol. Rev.|Pharmacological Reviews]]|volume=68|pages=49–75|doi=10.1124/pr.115.011106|pmid=26668301|vauthors=Jaisser F, Farman N|issue=1|doi-access=free}}</ref><ref>{{cite book|title = Human anatomy & physiology|last1 = Marieb|first1 = Elaine Nicpon|publisher = Pearson|year = 2013|location = Boston|pages = 629, Question 14|last2 = Hoehn|first2 = Katja|edition = 9th|oclc = 777127809|chapter = Chapter 16}}</ref> It is essential for [[sodium]] conservation in the kidney, salivary glands, sweat glands, and colon.<ref name=":0">{{cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK279079/|title=Endotext|last1=Arai|first1=Keiko|last2=Chrousos|first2=George P.|date=2000-01-01|publisher=MDText.com, Inc.|editor-last=De Groot|editor-first=Leslie J.|location=South Dartmouth (MA)|chapter=Aldosterone Deficiency and Resistance|pmid=25905305|editor2-last=Chrousos|editor2-first=George|editor3-last=Dungan|editor3-first=Kathleen|editor4-last=Feingold|editor4-first=Kenneth R.|editor5-last=Grossman|editor5-first=Ashley|editor6-last=Hershman|editor6-first=Jerome M.|editor7-last=Koch|editor7-first=Christian|editor8-last=Korbonits|editor8-first=Márta|editor9-last=McLachlan|editor9-first=Robert}}</ref> It plays a central role in the [[homeostasis|homeostatic]] regulation of [[blood pressure]], plasma [[sodium]] (Na⁺), and [[potassium]] (K⁺) levels. It does so primarily by acting on the mineralocorticoid receptors in the [[distal tubule]]s and [[collecting duct]]s of the [[nephron]].<ref name=":0" /> It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the [[kidney]], thereby indirectly influencing [[Water retention (medicine)|water retention]] or loss, [[blood pressure]], and [[blood volume]].<ref name="Marieb">Marieb Human Anatomy & Physiology 9th edition, chapter:16, page:629, question number:14</ref> When dysregulated, aldosterone is pathogenic and contributes to the development and progression of [[Cardiovascular disease|cardiovascular]] and [[kidney disease]].<ref>{{cite journal|last1=Gajjala|first1=Prathibha Reddy|last2=Sanati|first2=Maryam|last3=Jankowski|first3=Joachim|date=2015-07-08|title=Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes Mellitus and Cardiovascular Diseases as Its Comorbidities|journal=Frontiers in Immunology|volume=6|page=340|doi=10.3389/fimmu.2015.00340|issn=1664-3224|pmc=4495338|pmid=26217336|doi-access=free}}</ref> Aldosterone has exactly the opposite function of the [[atrial natriuretic hormone]] secreted by the [[heart]].<ref name="Marieb"/>

Aldosterone is part of the [[renin–angiotensin system|renin–angiotensin–aldosterone system]]. It has a [[plasma half-life]] of less than 20 minutes.<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK13300/|title=Pharmacokinetics of Corticosteroids|access-date=15 June 2016|year=2003}}</ref> Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like [[lisinopril]], which lowers blood pressure by blocking the [[angiotensin-converting enzyme]] (ACE), leading to lower aldosterone secretion. The net effect of these drugs is to reduce sodium and water retention but increase the retention of potassium. In other words, these drugs stimulate the excretion of sodium and water in urine, while they block the excretion of potassium.

Another example is [[spironolactone]], a [[potassium-sparing diuretic]] of the [[steroid]]al [[spirolactone]] group, which interferes with the aldosterone receptor (among others) leading to lower blood pressure by the mechanism described above.

Aldosterone was first isolated by [[Sylvia Agnes Sophia Tait|Sylvia Tait (Simpson)]] and [[James Francis Tait|Jim Tait]] in 1953; in collaboration with [[Tadeusz Reichstein]].<ref>{{cite journal |last1=Connell |first1=John M. C. |last2=Davies |first2=Eleanor |date=2005-07-01 |title=The new biology of aldosterone |url=https://joe.bioscientifica.com/view/journals/joe/186/1/1860001.xml |journal=Journal of Endocrinology |language=en-US |volume=186 |issue=1 |pages=1–20 |doi=10.1677/joe.1.06017 |pmid=16002531 |issn=0022-0795|doi-access=free }}</ref><ref>{{cite journal |last1=Tait |first1=Sylvia A.S |last2=Tait |first2=James F |last3=Coghlan |first3=John P |date=2004-03-31 |title=The discovery, isolation and identification of aldosterone: reflections on emerging regulation and function |url=https://linkinghub.elsevier.com/retrieve/pii/S0303720703003745 |journal=Molecular and Cellular Endocrinology |language=en |volume=217 |issue=1–2 |pages=1–21 |doi=10.1016/j.mce.2003.10.004|pmid=15134795 |s2cid=5738857 }}</ref><ref>{{cite journal |vauthors=Williams JS, Williams GH |title=50th anniversary of aldosterone |journal=J Clin Endocrinol Metab |volume=88 |issue=6 |pages=2364–72 |date=June 2003 |pmid=12788829 |doi=10.1210/jc.2003-030490 |doi-access=free }}</ref>

==Biosynthesis==

{{More citations needed section|date=December 2023}}

The [[corticosteroids]] are synthesized from [[cholesterol]] within the [[zona glomerulosa]] and zona fasciculata of [[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 pathways. The last parts are mediated either 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 an 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 glomerulosa]] and [[zona fasciculata]].

[[File:Steroidogenesis.svg|thumb|450px|[[Steroidogenesis]], showing aldosterone synthesis at upper-right corner.<ref name="HäggströmRichfield2014">{{cite journal|last2=Richfield|first2=David|year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|issn=2002-4436|last1=Häggström|first1=Mikael|doi-access=free}}</ref>]]

Aldosterone synthase is normally absent in other sections of the [[adrenal gland]].<ref>{{cite book |last=Barrett |first=Kim E. |url=https://www.worldcat.org/oclc/1076268769 |title=Ganong's review of medical physiology |date=2019 |others=Susan M. Barman, Heddwen L. Brooks, Jason X.-J. Yuan, William F. Preceded by: Ganong |isbn=9781260122404 |edition=26th |location=[New York] |pages=337 |oclc=1076268769}}</ref>

===Stimulation===

Aldosterone synthesis is stimulated by several factors:

* increase in the plasma concentration of angiotensin III, a metabolite of angiotensin II

* increase in [[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 [[renin]], a hormone secreted in the kidneys.

* Serum potassium concentrations are the most potent stimulator of aldosterone secretion.

* the [[ACTH stimulation test]], which is sometimes used to stimulate the production of aldosterone along with [[cortisol]] to determine whether primary or secondary [[adrenal insufficiency]] is present. However, ACTH has only a minor role in regulating aldosterone production; with hypopituitarism there is no atrophy of the zona glomerulosa.

* plasma [[acidosis]]

* the [[Mechanoreceptors|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.

* 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= 5|pages=1009–15 |date=May 1960 |pmid=13821632 |doi= 10.1161/01.CIR.21.5.1009|doi-access=free }}</ref>

The secretion of aldosterone has a [[Day|diurnal]] rhythm.<ref>{{cite journal |vauthors=[[Shelley Hurwitz|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 Appl Physiol |volume=96 |issue=4 |pages=1406–14 |date=April 2004 |pmid=14660513 |doi=10.1152/japplphysiol.00611.2003 }}</ref>

==Biological function==

Aldosterone is the primary of several endogenous members of the class of [[mineralocorticoid]]s in humans.{{Citation needed|date=November 2024}} [[Deoxycorticosterone]] is another important member of this class. Aldosterone tends to promote Na⁺ and water retention, and lower plasma K⁺ concentration by the following mechanisms:

# 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 upregulates and activates the [[basolateral]] [[Na+/K+-ATPase|Na⁺/K⁺ pumps]], which pumps three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates a concentration gradient which results in reabsorption of sodium (Na⁺) ions and water (which follows sodium) into the blood, and secreting potassium (K⁺) ions into the urine (lumen of collecting duct).

# Aldosterone upregulates epithelial sodium channels ([[ENaC]]s) in the [[Collecting duct system|collecting duct]] and the colon, increasing apical membrane permeability for Na⁺ and thus absorption.

# Cl⁻ is reabsorbed in conjunction with sodium cations to maintain the system's electrochemical balance.

# Aldosterone stimulates the secretion of K⁺ into the tubular lumen.<ref name="pmid10760062">{{cite journal|year=2000|last1=Palmer|first1=LG|last2=Frindt|first2=G|title=Aldosterone and potassium secretion by the cortical collecting duct|journal=Kidney International|volume=57|issue=4|pages=1324–8|pmid=10760062|doi=10.1046/j.1523-1755.2000.00970.x|doi-access=free}}</ref>

# Aldosterone stimulates Na⁺ and water reabsorption from the gut, salivary and sweat glands in exchange for K⁺.

# Aldosterone stimulates secretion of H⁺ via the H+/ATPase in the [[intercalated cells]] of the cortical collecting tubules

# Aldosterone upregulates expression of [[Sodium-chloride symporter|NCC]] in the distal convoluted tubule chronically and its activity acutely.<ref>{{cite journal|title = Aldosterone acutely stimulates NCC activity via a SPAK-mediated pathway|journal = American Journal of Physiology. Renal Physiology|date = 2013-09-01|issn = 1522-1466|pmc = 3761211|pmid = 23739593|pages = F645-652|volume = 305|issue = 5|doi = 10.1152/ajprenal.00053.2013|first1 = Benjamin|last1 = Ko|first2 = Abinash C.|last2 = Mistry|first3 = Lauren|last3 = Hanson|first4 = Rickta|last4 = Mallick|first5 = Brandi M.|last5 = Wynne|first6 = Tiffany L.|last6 = Thai|first7 = James L.|last7 = Bailey|first8 = Janet D.|last8 = Klein|first9 = Robert S.|last9 = Hoover}}</ref>

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 [[glomerular filtration rate]]s.<ref>{{cite book |author =Sherwood, Lauralee |title=Human physiology: from cells to systems |publisher=Brooks/Cole |location=Pacific Grove, CA |year=2001 |isbn=0-534-56826-2 |oclc= 43702042}}</ref>

Aldosterone, probably acting through mineralocorticoid receptors, may positively influence neurogenesis in the [[dentate gyrus]].<ref>{{cite journal |vauthors=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 |date=August 2002 |pmid=12176172 |doi= 10.1016/S0006-8993(02)03042-1|s2cid=24099239 }}</ref>

==Mineralocorticoid receptors==

[[Steroid receptor]]s are [[intracellular]] since steroid hormones are able to cross the cell membrane without a specific transporter. The aldosterone [[mineralocorticoid receptor]] (MR) 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 [[Protein subunit|subunits]] of the [[epithelial sodium channel]] (ENaC), the [[Na+/K+-ATPase|Na⁺/K⁺ pumps]] and their regulatory proteins [[serum and glucocorticoid-induced kinase]], and [[channel-inducing factor]], respectively.

The MR is stimulated by both aldosterone and cortisol, but a mechanism protects the body from excess aldosterone receptor stimulation by glucocorticoids (such as cortisol), which happen to be present at much higher concentrations than mineralocorticoids in the healthy individual. The mechanism consists of an enzyme called [[11-Beta hydroxysteroid dehydrogenase|11 β-hydroxysteroid dehydrogenase]] (11β-HSD). This enzyme co-localizes with intracellular adrenal steroid receptors and converts cortisol into cortisone, a relatively inactive metabolite with little affinity for the MR. [[Liquorice]], which contains [[glycyrrhetinic acid]], can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.

==Control of aldosterone release from the adrenal cortex==

[[File:Renin-angiotensin system in man shadow.svg|thumb|200px|The [[renin–angiotensin system]], showing role of aldosterone between the [[adrenal gland]]s and the [[kidney]]s<ref>Page 866-867 (Integration of Salt and Water Balance) and 1059 (The Adrenal Gland) in: {{cite book |author =Walter F. Boron |title=Medical Physiology: A Cellular And Molecular Approaoch |publisher=Elsevier/Saunders |year=2003 |pages=1300 |isbn=1-4160-2328-3 }}</ref>]]

===Major regulators===

====The role of the [[renin–angiotensin system]]====

Angiotensin is involved in regulating aldosterone and is the core regulation.<ref>{{cite journal |vauthors=Williams GH, Dluhy RG |title=Aldosterone biosynthesis. Interrelationship of regulatory factors |journal=Am J Med |volume=53 |issue=5 |pages=595–605 |date=November 1972 |pmid=4342886 |doi= 10.1016/0002-9343(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 |date=September 1982 |pmid=6286729 |pmc=370270 |doi= 10.1172/JCI110661}}</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 |vauthors=Messerli FH, Nowaczynski W, Honda M |title=Effects of angiotensin II on steroid metabolism and hepatic blood flow in man |journal=Circulation Research |volume=40 |issue=2 |pages=204–7 |date=February 1977 |pmid=844145 |doi= 10.1161/01.RES.40.2.204|display-authors=etal|doi-access=free }}</ref> When the blood flow decreases so does the destruction of aldosterone by liver enzymes.

Although sustained production of aldosterone requires persistent [[calcium]] entry through low-voltage-activated [[Calcium channel|Ca²⁺ channels]], isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit [[Calcium|Ca²⁺]] channels entry.<ref name="pmid22546854">{{cite journal|date=June 2012|title=Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electricaloscillators.|journal=J Clin Invest|volume=122|issue=6|pages=2046–2053|doi=10.1172/JCI61996|pmid=22546854|vauthors=Hu C, Rusin CG, Tan Z, Guagliardo NA, Barrett PQ|pmc=3966877}}</ref> However, mouse zona glomerulosa cells within adrenal slices spontaneously generate membrane potential oscillations of low periodicity; this innate electrical excitability of zona glomerulosa cells provides a platform for the production of a recurrent Ca²⁺ channels signal that can be controlled by [[angiotensin II]] and extracellular [[potassium]], the 2 major regulators of aldosterone production.<ref name="pmid22546854"/> [[Voltage-dependent calcium channel|Voltage-gated Ca²⁺ channel]]s have been detected in the zona glomerulosa of the human adrenal, which suggests that [[calcium channel blocker|Ca²⁺ channel blocker]]s may directly influence the adrenocortical biosynthesis of aldosterone in vivo.<ref name= "Felizola">{{cite journal|vauthors=Felizola SJ, Maekawa T, Nakamura Y, Satoh F, Ono Y, Kikuchi K, Aritomi S, Ikeda K, Yoshimura M, Tojo K, Sasano H | title=Voltage-gated calcium channels in the human adrenal and primary aldosteronism.|journal= J Steroid Biochem Mol Biol |volume= 144 |issue= part B |pages= 410–416 |year= 2014|doi = 10.1016/j.jsbmb.2014.08.012 |pmid= 25151951| s2cid=23622821|url= https://www.researchgate.net/publication/264979242}}</ref>

====The plasma concentration of [[potassium]]====

The amount of plasma renin secreted is an indirect function of the serum potassium<ref>{{cite journal |vauthors=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 |date=March 1979 |pmid=513492 |doi= 10.1038/ki.1979.37|doi-access=free }}</ref><ref>{{cite journal |vauthors=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 |date=June 1979 |pmid=222934 |doi= 10.1038/ki.1979.79|doi-access=free }}</ref> as probably determined by sensors in the carotid artery.<ref name="pmid13896654" /><ref>{{cite journal |vauthors=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= 5|pages=991–6 |date=May 1962 |pmid=13896654 |doi= 10.1152/ajplegacy.1962.202.5.991}}</ref>

====Adrenocorticotropic hormone====

[[Adrenocorticotropic hormone]] (ACTH), a pituitary peptide, also has some stimulating effect on aldosterone, probably by stimulating the formation of [[deoxycorticosterone]], a precursor of aldosterone.<ref>{{cite journal |vauthors=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 |date=June 1972 |pmid=4336939 |pmc=292278 |doi=10.1172/JCI106937 }}</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="pmid13590935" /> and possibly by further circumstances such as physical exertion, endotoxin shock, and burns.<ref name=Glaz>{{cite book |author1=Vecsei, Pál |author2=Gláz, Edith |title=Aldosterone |publisher=Pergamon Press |location=New York |year=1971 |isbn=0-08-013368-1 |oclc= 186705}}</ref><ref>{{cite journal |vauthors=Farrell GL, Rauschkolb EW |title=Evidence for diencephalic regulation of aldosterone secretion |journal=Endocrinology |volume=59 |issue=5 |pages=526–31 |date=November 1956 |pmid=13375573 |doi= 10.1210/endo-59-5-526}} on 529</ref>

===Miscellaneous regulators===

====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="pmid13896654">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="pmid13590935">{{cite journal |author =Farrell G |title=Regulation of aldosterone secretion |journal=Physiological Reviews |volume=38 |issue=4 |pages=709–28 |date=October 1958 |pmid=13590935 |doi= 10.1152/physrev.1958.38.4.709}}</ref> and probably emotion (anxiety, fear, and hostility)<ref name="pmid13449153">{{cite journal |vauthors=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 |date=August 1957 |pmid=13449153 |doi= 10.1210/jcem-17-8-1005}}</ref> (including [[surgical stress]]).<ref>{{cite journal |vauthors=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 |date=July 1952 |pmid=14934025 |pmc=1802239 |doi= 10.1097/00000658-195208000-00013}}</ref> Anxiety increases aldosterone,<ref name="pmid13449153" /> 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's 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-sensitive [[baroreceptor]]s are found in the vessel walls of nearly all large arteries in the thorax and neck, but are particularly plentiful in the sinuses of the carotid arteries and in the arch of the aorta. These specialized receptors are sensitive to changes in mean arterial pressure. An increase in sensed pressure results in an increased rate of firing by the baroreceptors and a negative feedback response, lowering systemic arterial pressure. Aldosterone release causes sodium and water retention, which causes increased blood volume, and a subsequent increase in blood pressure, which is sensed by the baroreceptors.<ref>Copstead, E. C. & Banasik, J. L. (2010.) Pathophysiology. (4th ed.). St. Louis, Mo: Saunders Elsevier.</ref> To maintain normal homeostasis these receptors also detect low blood pressure or low blood volume, causing aldosterone to be released. This results in sodium retention in the kidney, leading to water retention and increased blood volume.<ref>Marieb, E. N. (2004) Human anatomy and physiology (6th ed) San Francisco: Pearson Benjamin Cummings.</ref>

<!--====The role of the [[juxtaglomerular apparatus]]====

Through the [[renin–angiotensin system]].

{{Expand section|Mechanism of Action|date=December 2009}}

-->

====The plasma concentration of [[sodium]]====

Aldosterone levels vary as an [[inverse function]] of sodium intake as sensed via osmotic pressure.<ref>{{cite journal |vauthors=Schneider EG, Radke KJ, Ulderich DA, Taylor RE |title=Effect of osmolality on aldosterone secretion |journal=Endocrinology |volume=116 |issue=4 |pages=1621–6 |date=April 1985 |pmid=3971930 |doi= 10.1210/endo-116-4-1621}}</ref> The slope of the response of aldosterone to serum potassium is almost independent of sodium intake.<ref>{{cite journal |vauthors=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 |date=August 1972 |pmid=5054456 |pmc=292351 |doi=10.1172/JCI107001 }}</ref> Aldosterone is 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, potassium is strongly regulated at all sodium intakes by aldosterone when the supply of potassium is adequate, which it usually is in "primitive" diets.

===Aldosterone feedback===

Feedback by aldosterone concentration itself is of a nonmorphological 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/>

==Associated clinical conditions==

[[Hyperaldosteronism]] is abnormally increased levels of aldosterone, while [[hypoaldosteronism]] is abnormally decreased levels of aldosterone.

A measurement of aldosterone in blood may be termed a ''plasma aldosterone concentration'' (''PAC''), which may be compared to [[plasma renin activity]] (PRA) as an [[aldosterone-to-renin ratio]].

===Hyperaldosteronism===

[[Primary aldosteronism]], also known as ''primary hyperaldosteronism'', is characterized by the overproduction of aldosterone by the [[adrenal gland]]s,<ref name=conn>{{cite journal |vauthors=Conn JW, Louis LH |title=Primary aldosteronism: a new clinical entity |journal=Trans. Assoc. Am. Physicians |volume=68 |pages=215–31; discussion, 231–3 |year=1955 |pmid=13299331 }}</ref> when not a result of excessive renin secretion. It leads to [[arterial hypertension]] (high blood pressure) associated with hypokalemia, usually a diagnostic clue. [[Secondary hyperaldosteronism]], on the other hand, is due to overactivity of the [[renin–angiotensin system]].

[[Conn's syndrome]] is primary hyperaldosteronism caused by an aldosterone-producing adenoma.

Depending on cause and other factors, hyperaldosteronism can be treated by surgery and/or medically, such as by [[aldosterone antagonist]]s.

The ratio of renin to aldosterone is an effective screening test to screen for primary hyperaldosteronism related to [[adrenal adenoma]]s.<ref>{{cite journal |last1=Rayner |first1=BL |title=The aldosterone/renin ratio as a screening test for primary aldosteronism. |journal=S Afr Med J |year=2000 |volume=90 |issue=4 |pages=394–400 |pmid=10957926 }}</ref><ref>{{cite journal |last1=Ducher |first1=M |last2=Mounier-Véhier |first2=C |last3=Baguet |first3=JP |last4=Tartière |first4=JM |last5=Sosner |first5=P |last6=Régnier-Le Coz |first6=S |last7=Perez |first7=L |last8=Fourcade |first8=J |last9=Jabourek |first9=O |last10=Lejeune |first10=S |last11=Stolz |first11=A |last12=Fauvel |first12=JP |title=Aldosterone-to-renin ratio for diagnosing aldosterone-producing adenoma: a multicentre study. |journal=Archives of Cardiovascular Diseases |date=December 2012 |volume=105 |issue=12 |pages=623–30 |doi=10.1016/j.acvd.2012.07.006 |pmid=23199617|doi-access=free }}</ref> It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism.<ref name="renin">{{cite journal |last1=Hoffman |first1=Robert |title=What is the role of aldosterone-to-renin ratio (ARR) in the diagnosis of hyperaldosteronism? |website=www.medscape.com |date=October 19, 2018 |url=https://www.medscape.com/answers/920713-68762/what-is-the-role-of-aldosterone-to-renin-ratio-arr-in-the-diagnosis-of-hyperaldosteronism |access-date=18 May 2019}}</ref> Blood obtained when the patient has been standing for more than 2 hours are more sensitive than those from when the patient is lying down. Before the test, individuals should not restrict salt and [[hypokalemia|low potassium]] should be corrected before the test because it can suppress aldosterone secretion.<ref name="renin"/>

===Hypoaldosteronism===

An [[ACTH stimulation test#Aldosterone stimulation|ACTH stimulation test for aldosterone]] can help in determining the cause of [[hypoaldosteronism]], with a low aldosterone response indicating a primary hypoaldosteronism of the adrenals, while a large response indicating a secondary hypoaldosteronism.

The most common cause of this condition (and related symptoms) is [[Addison's disease]]; it is typically treated by [[fludrocortisone]], which has a much longer persistence (1 day) in the bloodstream.

==Additional images==

<gallery>

Image:Corticosteroid-biosynthetic-pathway-rat.png|Corticosteroid biosynthetic pathway in rat

Image:Corticosterone.svg|[[Corticosterone]]

</gallery>

==References==

{{Reflist}}

{{Hormones}}

{{Endogenous steroids}}

{{Renal physiology}}

{{Mineralocorticoids and antimineralocorticoids}}

{{Mineralocorticoid receptor modulators}}

{{Estrogen receptor modulators}}

{{Authority control}}

[[Category:Aldehydes]]

[[Category:GPER agonists]]

[[Category:Mineralocorticoids]]

[[Category:Pregnanes]]

[[Category:Steroid hormones]]

[[Category:Triketones]]

[[Category:Enones]]