Etiocholanolone

{{Short description|Chemical compound}}

{{Drugbox

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| verifiedrevid = 413760240

| IUPAC_name = (3R,5R,8R,9S,10S,13S,14S)-3-Hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one

| image = Etiocholanolone.svg

| image_class = skin-invert-image

| alt = Skeletal formula of etiocholanolone

| image2 = Etiocholanolone 3D ball.png

| alt2 = Ball-and-stick model of the etiocholanolone molecule

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 53-42-9

| ATC_prefix = none

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| PubChem = 5880

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB02854

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 97CGB1M48I

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 28195

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| ChEMBL = 85799

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 5669

| C=19 | H=30 | O=2

| synonyms = Aetiocholanolone
5-Isoandrosterone

| smiles = [H][C@]12CC[C@@]3([H])[C@]4([H])CCC(=O)[C@@]4(C)CC[C@]3([H])[C@@]1(C)CC[C@@H](O)C2

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C19H30O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12-16,20H,3-11H2,1-2H3/t12-,13-,14+,15+,16+,18+,19+/m1/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = QGXBDMJGAMFCBF-BNSUEQOYSA-N

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Etiocholanolone, also known as 5β-androsterone, as well as 3α-hydroxy-5β-androstan-17-one or etiocholan-3α-ol-17-one, is an etiocholane (5β-androstane) steroid as well as an endogenous 17-ketosteroid that is produced from the metabolism of testosterone. It causes fever, immunostimulation, and leukocytosis, and is used to evaluate adrenal cortex function, bone marrow performance, and in neoplastic disease to stimulate the immune system. Etiocholanolone is also known to be an inhibitory androstane neurosteroid,{{cite book | author = Reddy DS | title = Sex Differences in the Human Brain, their Underpinnings and Implications | chapter = Neurosteroids | journal = Prog. Brain Res. | volume = 186 | pages = 113–37 | year = 2010 | pmid = 21094889 | pmc = 3139029 | doi = 10.1016/B978-0-444-53630-3.00008-7 | series = Progress in Brain Research | isbn = 9780444536303 }} acting as a positive allosteric modulator of the GABAA receptor,{{cite journal | vauthors = Li P, Bracamontes J, Katona BW, Covey DF, Steinbach JH, Akk G | title = Natural and enantiomeric etiocholanolone interact with distinct sites on the rat alpha1beta2gamma2L GABAA receptor | journal = Molecular Pharmacology | volume = 71 | issue = 6 | pages = 1582–1590 | date = June 2007 | pmid = 17341652 | pmc = 3788649 | doi = 10.1124/mol.106.033407 | s2cid = 44286086 }} and possesses anticonvulsant effects.{{cite journal | vauthors = Kaminski RM, Marini H, Kim WJ, Rogawski MA | title = Anticonvulsant activity of androsterone and etiocholanolone | journal = Epilepsia | volume = 46 | issue = 6 | pages = 819–827 | date = June 2005 | pmid = 15946323 | pmc = 1181535 | doi = 10.1111/j.1528-1167.2005.00705.x }} The unnatural enantiomer of etiocholanolone is more potent as a positive allosteric modulator of GABAA receptors and as an anticonvulsant than the natural form.{{cite journal | vauthors = Zolkowska D, Dhir A, Krishnan K, Covey DF, Rogawski MA | title = Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms | journal = Psychopharmacology | volume = 231 | issue = 17 | pages = 3325–3332 | date = September 2014 | pmid = 24705905 | pmc = 4134984 | doi = 10.1007/s00213-014-3546-x }}

Etiocholanolone has been studied as a pyrogenic steroid in the so-called steroid fever (or etiocholanolone fever),{{cite journal | vauthors = Heckel GP |title= Steroid fever |journal=The Lancet |date=April 1963 |volume=281 |issue=7285 |pages=835–836 |doi=10.1016/S0140-6736(63)91549-6}}{{cite journal | vauthors = Kappas A, Palmer RH | title = Novel biological properties of steroid metabolites; fever-production in man | journal = Journal of the Reticuloendothelial Society | volume = 4 | issue = 4 | pages = 231–236 | date = July 1967 | pmid = 6056839 }} a condition similar to familial mediterranean fever (FMF). Etiocholanolone (like pregnanolone) activates the pyrin inflammasome.{{cite journal | vauthors = Magnotti F, Chirita D, Dalmon S, Martin A, Bronnec P, Sousa J, Helynck O, Lee W, Kastner DL, Chae JJ, McDermott MF, Belot A, Popoff M, Sève P, Georgin-Lavialle S, Munier-Lehmann H, Tran TA, De Langhe E, Wouters C, Jamilloux Y, Henry T | display-authors = 6 | title = Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism | journal = Cell Reports | volume = 41 | issue = 2 | pages = 111472 | date = October 2022 | pmid = 36223753 | doi = 10.1016/j.celrep.2022.111472|biorxiv=10.1101/2021.10.29.466454 | pmc = 9626387 | s2cid = 240345817 | doi-access=free }} It is not known whether these endogenous steroids play a role in triggering FMF flares but they may make a link between stress, menstrual cycle and disease flares.{{cite journal | vauthors = Karadag O, Tufan A, Yazisiz V, Ureten K, Yilmaz S, Cinar M, Akdogan A, Erdem H, Ozturk MA, Pay S, Dinc A | display-authors = 6 | title = The factors considered as trigger for the attacks in patients with familial Mediterranean fever | journal = Rheumatology International | volume = 33 | issue = 4 | pages = 893–897 | date = April 2013 | pmid = 22814791 | doi = 10.1007/s00296-012-2453-x | s2cid = 25599588 }}{{cite journal | vauthors = Akar S, Soyturk M, Onen F, Tunca M | title = The relations between attacks and menstrual periods and pregnancies of familial Mediterranean fever patients | journal = Rheumatology International | volume = 26 | issue = 7 | pages = 676–679 | date = May 2006 | pmid = 16184383 | doi = 10.1007/s00296-005-0041-z | s2cid = 1617088 }}

Etiocholanolone is produced from 5β-dihydrotestosterone, with 3α,5β-androstanediol as an intermediate.

Chemistry

{{See also|List of neurosteroids}}

See also

References