Jump to content

11α-Hydroxyprogesterone: Difference between revisions

Edit links
From Wikipedia, the free encyclopedia
Browse history interactively
Content deleted Content added
VisualWikitext
←Created page with '{{Drugbox | Verifiedfields = | Watchedfields = | verifiedrevid = | IUPAC_name = (8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11...'
 
rm "recently"
 
(40 intermediate revisions by 21 users not shown)
Line 1: Line 1:
{{Short description|Chemical compound}}
{{Distinguish|17α-hydroxyprogesterone}}
{{Drugbox
{{Drugbox
| Verifiedfields =
| Verifiedfields =
| Watchedfields =
| Watchedfields =
| verifiedrevid =
| verifiedrevid =
| IUPAC_name = (8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
| IUPAC_name = (8''S'',9''S'',10''R'',11''R'',13''S'',14''S'',17''S'')-17-acetyl-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[''a'']phenanthren-3-one
| image =
| image = 11α-Hydroxyprogesterone.svg
| width =
| width = 225px


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
Line 24: Line 26:
| metabolism =
| metabolism =
| elimination_half-life =
| elimination_half-life =
| excretion =
| excretion =


<!-- Identifiers -->
<!-- Identifiers -->
| CAS_number_Ref =
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 80-75-1
| CAS_number = 80-75-1
| CAS_supplemental =
| CAS_supplemental =
Line 39: Line 41:
| DrugBank =
| DrugBank =
| ChemSpiderID_Ref =
| ChemSpiderID_Ref =
| ChemSpiderID = 389106
| ChemSpiderID = 83709
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII =
| UNII = D8X4JXL4VM
| KEGG =
| KEGG =
| ChEBI = 16076
| ChEBI = 16076
| ChEMBL = 1563246
| ChEMBL = 1563246
⚫
| synonyms = 11α-OHP; 11α-Hydroxypregn-4-ene-3,20-dione; 4-Pregnen-11α-ol-3,20-dione; δ<sup>4</sup>-Pregnen-11α-ol-3,20-dione


<!--Chemical data-->
<!--Chemical data-->
| C=21 | H=30 | O=3
| C=21 | H=30 | O=3
⚫
| SMILES = CC(=O)C1CCC2C1(CC(C3C2CCC4=CC(=O)CCC34C)O)C
| molecular_weight = 330.4611 g/mol
⚫
| smiles = CC(=O)C1CCC2C1(CC(C3C2CCC4=CC(=O)CCC34C)O)C
| StdInChI_Ref =
| StdInChI_Ref =
| StdInChI = 1S/C21H30O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-19,24H,4-9,11H2,1-3H3/t15-,16+,17-,18+,19+,20-,21+/m0/s1
| StdInChI = 1S/C21H30O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-19,24H,4-9,11H2,1-3H3/t15-,16+,17-,18+,19+,20-,21+/m0/s1
| StdInChIKey_Ref =
| StdInChIKey_Ref =
| StdInChIKey = BFZHCUBIASXHPK-QJSKAATBSA-N
| StdInChIKey = BFZHCUBIASXHPK-QJSKAATBSA-N
⚫
| synonyms = 11α-Hydroxypregn-4-ene-3,20-dione; 4-Pregnen-11α-ol-3,20-dione; δ<sup>4</sup>-Pregnen-11α-ol-3,20-dione
}}
}}


'''11α-Hydroxyprogesterone''' ('''11α-OHP'''), or '''11α-hydroxypregn-4-ene-3,20-dione''' is an [[endogenous]] [[steroid]] and [[metabolite]] of [[progesterone]].<ref name="Ford1954">{{cite journal|last1=Ford|first1=Donald H.|title=EFFECT OF 11α-HYDROXYPROGESTERONE ON REPRODUCTIVE SYSTEM OF NORMAL AND PREGNANT ADULT WISTAR RATS*|journal=The Journal of Clinical Endocrinology & Metabolism|volume=14|issue=10|year=1954|pages=1268–1270|issn=0021-972X|doi=10.1210/jcem-14-10-1268}}</ref><ref name="pmid7895695">{{cite journal | vauthors = Souness GW, Latif SA, Laurenzo JL, Morris DJ | title = 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat | journal = Endocrinology | volume = 136 | issue = 4 | pages = 1809–12 | year = 1995 | pmid = 7895695 | doi = 10.1210/endo.136.4.7895695 | url = }}</ref><ref name="pmid8698448">{{cite journal | vauthors = Souness GW, Morris DJ | title = 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat | journal = Hypertension | volume = 27 | issue = 3 Pt 1 | pages = 421–5 | year = 1996 | pmid = 8698448 | doi = | url = }}</ref> It is a weak [[antiandrogen]], and is devoid of [[androgen]]ic, [[estrogen]]ic, and [[progestogen]]ic activity.<ref name="Lerner1975">{{cite journal|last1=Lerner|first1=Leonard J.|title=Androgen antagonists|journal=Pharmacology & Therapeutics. Part B: General and Systematic Pharmacology|volume=1|issue=2|year=1975|pages=217–231|issn=0306039X|doi=10.1016/0306-039X(75)90006-9|quote=11α Hydroxyprogesterone, while devoid of androgenic, estrogenic and progestational activity, is weakly anti androgenic in castrate rats.}}</ref><ref name="NguyenVirus2012">{{cite journal|last1=Nguyen|first1=Kim Thoa|last2=Virus|first2=Cornelia|last3=Günnewich|first3=Nils|last4=Hannemann|first4=Frank|last5=Bernhardt|first5=Rita|title=Changing the Regioselectivity of a P450 from C15 to C11 Hydroxylation of Progesterone|journal=ChemBioChem|volume=13|issue=8|year=2012|pages=1161–1166|issn=14394227|doi=10.1002/cbic.201100811|quote=11α-Hydroxyprogesterone is an important pharmaceutical compound with anti-androgenic and blood-pressure-regulating activity. [...] 11α-Hydroxyprogesterone can therefore influence blood pressure regulation.12 Furthermore, 11α-hydroxyprogesterone exhibits an anti-androgenic activity with minimal estrogenic and progestational side effects.13 This substance was also recently patented for its role in treating skin diseases, especially for psoriasis in combination with clobetasol propionate and minoxidil.14.}}</ref><ref name="TindallChang1984">{{cite journal|last1=Tindall|first1=D.J.|last2=Chang|first2=C.H.|last3=Lobl|first3=T.J.|last4=Cunningham|first4=G.R.|title=Androgen antagonists in androgen target tissues|journal=Pharmacology & Therapeutics|volume=24|issue=3|year=1984|pages=367–400|issn=01637258|doi=10.1016/0163-7258(84)90010-X}}</ref> For this reason, it was investigated as a [[topical administration|topical]] antiandrogen in the early 1950s, and was found to produce some benefit.<ref name="Millikan2016">{{cite book|author=Larry E. Millikan|title=Drug Therapy in Dermatology|url=http://books.google.com/books?id=3TDMBQAAQBAJ&pg=PA403|date=19 April 2016|publisher=CRC Press|isbn=978-0-203-90831-0|page=403|quote=Topical antiandrogens have also been tried, including topical progesterone, which proved ineffective. However, small studies with topical 11α-hydroxyprogesterone and 17α-estradiol showed some benefit [38,39].}}</ref> In 1995, 11α-OHP, along with its [[structural analog|analogue]] [[11β-hydroxyprogesterone]], was identified as a very potent [[competitive inhibitor|competitive]] [[enzyme inhibitor|inhibitor]] of both [[isoform]]s ([[11β-hydroxysteroid dehydrogenase type 1|1]] and [[Corticosteroid 11-beta-dehydrogenase isozyme 2|2]]) of [[11β-hydroxysteroid dehydrogenase]] (11β-HSD).<ref name="pmid7895695" /><ref name="pmid8698448" /> It is notably not metabolized by 11β-HSD2.<ref name="MoritaZhou1996" /> 11α-OHP is a more potent inhibitor of 11β-HSD than [[enoxolone]] (glycyrrhetinic acid) and [[carbenoxolone]] ''[[in vitro]]'' ([[IC50|IC<sub>50</sub>]] = 0.9 nM; IC<sub>50</sub> = 5 nM in transfected cells).<ref name="TomlinsonWalker2004">{{cite journal|last1=Tomlinson|first1=Jeremy W.|last2=Walker|first2=Elizabeth A.|last3=Bujalska|first3=Iwona J.|last4=Draper|first4=Nicole|last5=Lavery|first5=Gareth G.|last6=Cooper|first6=Mark S.|last7=Hewison|first7=Martin|last8=Stewart|first8=Paul M.|title=11β-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response|journal=Endocrine Reviews|volume=25|issue=5|year=2004|pages=831–866|issn=0163-769X|doi=10.1210/er.2003-0031|quote=In intact cells 11α-hydroxyprogesterone is a more potent inhibitor of 11β-HSD1 than glycyrrhetinic acid or 11β-hydroxyprogesterone (117, 118).}}</ref><ref name="MoritaZhou1996">{{cite journal|last1=Morita|first1=H|last2=Zhou|first2=M|last3=Foecking|first3=M F|last4=Gomez-Sanchez|first4=E P|last5=Cozza|first5=E N|last6=Gomez-Sanchez|first6=C E|title=11 beta-Hydroxysteroid dehydrogenase type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11 alpha-hydroxyprogesterone.|journal=Endocrinology|volume=137|issue=6|year=1996|pages=2308–2314|issn=0013-7227|doi=10.1210/endo.137.6.8641180|quote=11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM).}}</ref><ref name="BujalskaShimojo1997">{{cite journal|last1=Bujalska|first1=Iwona|last2=Shimojo|first2=Masako|last3=Howie|first3=Alex|last4=Stewart|first4=Paul M.|title=Human 11β-hydroxysteroid dehydrogenase: Studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue|journal=Steroids|volume=62|issue=1|year=1997|pages=77–82|issn=0039128X|doi=10.1016/S0039-128X(96)00163-8}}</ref> The compound has been found to be highly active in conferring [[mineralocorticoid]] [[sodium]]-retaining activity of [[corticosterone]] ''[[in vivo]]'' in rat [[bioassay]]s and in increasing [[blood pressure]], effects that it mediates by preventing the 11β-mediated inactivation of endogenous mineralocorticoids.<ref name="pmid7895695" /><ref name="pmid8698448" /> Because of its inhibition of 11β-HSD and consequent potentiation of [[corticosteroid]]s, 11α-OHP has recently been patented for the treatment of [[skin disease]]s, particularly [[psoriasis]] in combination with [[clobetasol propionate]] and [[minoxidil]].<ref name="NguyenVirus2012" />
'''11α-Hydroxyprogesterone''' ('''11α-OHP'''), or '''11α-hydroxypregn-4-ene-3,20-dione''' is an [[endogenous]] [[steroid]] and [[metabolite]] of [[progesterone]].<ref name="Ford1954">{{cite journal | vauthors = Ford DH | title = Effect of 11 alpha-hydroxyprogesterone on reproductive system of normal and pregnant adult wistar rats | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 14 | issue = 10 | pages = 1268–1270 | date = October 1954 | pmid = 13201630 | doi = 10.1210/jcem-14-10-1268 }}</ref><ref name="pmid7895695">{{cite journal | vauthors = Souness GW, Latif SA, Laurenzo JL, Morris DJ | title = 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat | journal = Endocrinology | volume = 136 | issue = 4 | pages = 1809–1812 | date = April 1995 | pmid = 7895695 | doi = 10.1210/endo.136.4.7895695 }}</ref><ref name="pmid8698448">{{cite journal | vauthors = Souness GW, Morris DJ | title = 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat | journal = Hypertension | volume = 27 | issue = 3 Pt 1 | pages = 421–425 | date = March 1996 | pmid = 8698448 | doi = 10.1161/01.hyp.27.3.421 }}</ref> It is a weak [[antiandrogen]], and is devoid of [[androgen]]ic, [[estrogen]]ic, and [[progestogen]]ic activity.<ref name="Lerner1975">{{cite journal | vauthors = Lerner LJ | title = Androgen antagonists | journal = Pharmacology & Therapeutics B | volume = 1 | issue = 2 | pages = 217–231 | year = 1975 | pmid = 772705 | doi = 10.1016/0306-039X(75)90006-9 | quote = 11α Hydroxyprogesterone, while devoid of androgenic, estrogenic and progestational activity, is weakly anti androgenic in castrate rats. }}</ref><ref name="NguyenVirus2012">{{cite journal | vauthors = Nguyen KT, Virus C, Günnewich N, Hannemann F, Bernhardt R | title = Changing the regioselectivity of a P450 from C15 to C11 hydroxylation of progesterone | journal = ChemBioChem | volume = 13 | issue = 8 | pages = 1161–1166 | date = May 2012 | pmid = 22532270 | doi = 10.1002/cbic.201100811 | quote = 11α-Hydroxyprogesterone is an important pharmaceutical compound with anti-androgenic and blood-pressure-regulating activity. [...] 11α-Hydroxyprogesterone can therefore influence blood pressure regulation.12 Furthermore, 11α-hydroxyprogesterone exhibits an anti-androgenic activity with minimal estrogenic and progestational side effects.13 This substance has been proposed for treating skin diseases, especially for psoriasis in combination with clobetasol propionate and minoxidil.14. | s2cid = 34483686 }}</ref><ref name="TindallChang1984">{{cite journal | vauthors = Tindall DJ, Chang CH, Lobl TJ, Cunningham GR | title = Androgen antagonists in androgen target tissues | journal = Pharmacology & Therapeutics | volume = 24 | issue = 3 | pages = 367–400 | year = 1984 | pmid = 6205409 | doi = 10.1016/0163-7258(84)90010-X }}</ref>


11α-OHP was investigated as a [[topical administration|topical]] antiandrogen for the treatment of [[androgen-dependent condition|androgen-dependent]] [[skin condition]]s in the early 1950s, and was found to produce some benefit.<ref name="Millikan2016">{{cite book| vauthors = Millikan LE |title=Drug Therapy in Dermatology|url=https://books.google.com/books?id=3TDMBQAAQBAJ&pg=PA403|date=19 April 2016|publisher=CRC Press|isbn=978-0-203-90831-0|page=403|quote=Topical antiandrogens have also been tried, including topical progesterone, which proved ineffective. However, small studies with topical 11α-hydroxyprogesterone and 17α-estradiol showed some benefit [38,39].}}</ref> In 1995, 11α-OHP, along with its [[epimer]] [[11β-hydroxyprogesterone]], was identified as a very potent [[competitive inhibitor|competitive]] [[enzyme inhibitor|inhibitor]] of both [[isoform]]s ([[11β-hydroxysteroid dehydrogenase type 1|1]] and [[Corticosteroid 11-beta-dehydrogenase isozyme 2|2]]) of [[11β-hydroxysteroid dehydrogenase]] (11β-HSD).<ref name="pmid7895695" /><ref name="pmid8698448" /> It is notably not metabolized by 11β-HSD2.<ref name="MoritaZhou1996" />
⚫
11α-OHP is used as a [[precursor (chemistry)|precursor]] in the [[chemical synthesis|chemical syntheses]] of [[cortisone]] and [[hydrocortisone]].<ref name="DunnWells2010">{{cite book|author1=Peter J. Dunn|author2=Andrew Wells|author3=Michael T. Williams|title=Green Chemistry in the Pharmaceutical Industry|url=http://books.google.com/books?id=sZP_bQifwc8C&pg=PA2|date=2 February 2010|publisher=John Wiley & Sons|isbn=978-3-527-62969-5|pages=2–}}</ref><ref name="LamberthDinges2016">{{cite book|author1=Clemens Lamberth|author2=Jürgen Dinges|title=Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals|url=http://books.google.com/books?id=Bc8vDAAAQBAJ&pg=PA250|date=17 May 2016|publisher=Wiley|isbn=978-3-527-69396-2|pages=250–}}</ref><ref name="RamawatMérillon2008">{{cite book|author1=Kishan Gopal Ramawat|author2=Jean-Michel Mérillon|title=Bioactive Molecules and Medicinal Plants|url=http://books.google.com/books?id=rchJAAAAQBAJ&pg=PA5|date=16 October 2008|publisher=Springer Science & Business Media|isbn=978-3-540-74603-4|pages=5–}}</ref>


11α-OHP is a more potent inhibitor of 11β-HSD than [[enoxolone]] (glycyrrhetinic acid) or [[carbenoxolone]] ''[[in vitro]]'' ([[IC50|IC<sub>50</sub>]] = 0.9 nM; IC<sub>50</sub> = 5 nM in transfected cells).<ref name="MoritaZhou1996">{{cite journal | vauthors = Morita H, Zhou M, Foecking MF, Gomez-Sanchez EP, Cozza EN, Gomez-Sanchez CE | title = 11 beta-Hydroxysteroid dehydrogenase type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11 alpha-hydroxyprogesterone | journal = Endocrinology | volume = 137 | issue = 6 | pages = 2308–2314 | date = June 1996 | pmid = 8641180 | doi = 10.1210/endo.137.6.8641180 | quote = 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM). | doi-access = free }}</ref><ref name="TomlinsonWalker2004">{{cite journal | vauthors = Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM | display-authors = 6 | title = 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response | journal = Endocrine Reviews | volume = 25 | issue = 5 | pages = 831–866 | date = October 2004 | pmid = 15466942 | doi = 10.1210/er.2003-0031 | quote = In intact cells 11α-hydroxyprogesterone is a more potent inhibitor of 11β-HSD1 than glycyrrhetinic acid or 11β-hydroxyprogesterone (117, 118). | doi-access = free }}</ref><ref name="BujalskaShimojo1997">{{cite journal | vauthors = Bujalska I, Shimojo M, Howie A, Stewart PM | title = Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue | journal = Steroids | volume = 62 | issue = 1 | pages = 77–82 | date = January 1997 | pmid = 9029719 | doi = 10.1016/S0039-128X(96)00163-8 | s2cid = 22551136 }}</ref> The compound has been found to be highly active in conferring [[mineralocorticoid]] [[sodium]]-retaining activity of [[corticosterone]] ''[[in vivo]]'' in rat [[bioassay]]s and in increasing [[blood pressure]], effects that it mediates by preventing the 11β-HSD-mediated inactivation of endogenous [[corticosteroid]]s.<ref name="pmid7895695" /><ref name="pmid8698448" />
⚫
==References==
⚫
{{Reflist|2}}


⚫
11α-OHP is used as a [[precursor (chemistry)|precursor]] in [[chemical synthesis|chemical syntheses]] of [[cortisone]] and [[hydrocortisone]].<ref name="DunnWells2010">{{cite book| vauthors = Dunn PJ, Wells A, Williams MT |title=Green Chemistry in the Pharmaceutical Industry|url=https://books.google.com/books?id=sZP_bQifwc8C&pg=PA2|date=2 February 2010|publisher=John Wiley & Sons|isbn=978-3-527-62969-5|pages=2–}}</ref><ref name="LamberthDinges2016">{{cite book| vauthors = Lamberth C, Dinges J |title=Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals|url=https://books.google.com/books?id=Bc8vDAAAQBAJ&pg=PA250|date=17 May 2016|publisher=Wiley|isbn=978-3-527-69396-2|pages=250–}}</ref><ref name="RamawatMérillon2008">{{cite book| vauthors = Ramawat KG, Mérillon JM |title=Bioactive Molecules and Medicinal Plants|url=https://books.google.com/books?id=rchJAAAAQBAJ&pg=PA5|date=16 October 2008|publisher=Springer Science & Business Media|isbn=978-3-540-74603-4|pages=5–}}</ref>


== See also ==
* [[Steroidal antiandrogen]]
* [[List of steroidal antiandrogens]]
* [[Glycyrrhizin]]

⚫
== References ==
⚫
{{Reflist|30em}}

{{Endogenous steroids}}
{{Androgen receptor modulators}}
{{Androgen receptor modulators}}
{{Steroid hormone metabolism modulators}}


{{DEFAULTSORT:Hydroxyprogesterone, 11α-}}
⚫
[[Category:11β-HSD inhibitors]]
⚫
[[Category:Antiandrogens]]
⚫
[[Category:Hormonal agents]]
⚫
[[Category:Steroids]]


⚫
[[Category:11β-Hydroxysteroid dehydrogenase inhibitors]]
⚫
[[Category:Cyclohexanols]]
⚫
[[Category:Diketones]]
[[Category:Pregnanes]]
[[Category:Steroidal antiandrogens]]
⚫
[[Category:Enones]]


{{steroid-stub}}
{{steroid-stub}}

Latest revision as of 13:23, 29 May 2024

Not to be confused with 17α-hydroxyprogesterone.
11α-Hydroxyprogesterone
Clinical data
Other names11α-OHP; 11α-Hydroxypregn-4-ene-3,20-dione; 4-Pregnen-11α-ol-3,20-dione; δ4-Pregnen-11α-ol-3,20-dione
Identifiers
  • (8S,9S,10R,11R,13S,14S,17S)-17-acetyl-11-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.189 Edit this at Wikidata
Chemical and physical data
FormulaC21H30O3
Molar mass330.468 g·mol−1
3D model (JSmol)
  • CC(=O)C1CCC2C1(CC(C3C2CCC4=CC(=O)CCC34C)O)C
  • InChI=1S/C21H30O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-19,24H,4-9,11H2,1-3H3/t15-,16+,17-,18+,19+,20-,21+/m0/s1
  • Key:BFZHCUBIASXHPK-QJSKAATBSA-N

11α-Hydroxyprogesterone (11α-OHP), or 11α-hydroxypregn-4-ene-3,20-dione is an endogenous steroid and metabolite of progesterone.[1][2][3] It is a weak antiandrogen, and is devoid of androgenic, estrogenic, and progestogenic activity.[4][5][6]

11α-OHP was investigated as a topical antiandrogen for the treatment of androgen-dependent skin conditions in the early 1950s, and was found to produce some benefit.[7] In 1995, 11α-OHP, along with its epimer 11β-hydroxyprogesterone, was identified as a very potent competitive inhibitor of both isoforms (1 and 2) of 11β-hydroxysteroid dehydrogenase (11β-HSD).[2][3] It is notably not metabolized by 11β-HSD2.[8]

11α-OHP is a more potent inhibitor of 11β-HSD than enoxolone (glycyrrhetinic acid) or carbenoxolone in vitro (IC50 = 0.9 nM; IC50 = 5 nM in transfected cells).[8][9][10] The compound has been found to be highly active in conferring mineralocorticoid sodium-retaining activity of corticosterone in vivo in rat bioassays and in increasing blood pressure, effects that it mediates by preventing the 11β-HSD-mediated inactivation of endogenous corticosteroids.[2][3]

11α-OHP is used as a precursor in chemical syntheses of cortisone and hydrocortisone.[11][12][13]

See also

[edit]

References

[edit]
  1. ^ Ford DH (October 1954). "Effect of 11 alpha-hydroxyprogesterone on reproductive system of normal and pregnant adult wistar rats". The Journal of Clinical Endocrinology and Metabolism. 14 (10): 1268–1270. doi:10.1210/jcem-14-10-1268. PMID 13201630.
  2. ^ a b c Souness GW, Latif SA, Laurenzo JL, Morris DJ (April 1995). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat". Endocrinology. 136 (4): 1809–1812. doi:10.1210/endo.136.4.7895695. PMID 7895695.
  3. ^ a b c Souness GW, Morris DJ (March 1996). "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat". Hypertension. 27 (3 Pt 1): 421–425. doi:10.1161/01.hyp.27.3.421. PMID 8698448.
  4. ^ Lerner LJ (1975). "Androgen antagonists". Pharmacology & Therapeutics B. 1 (2): 217–231. doi:10.1016/0306-039X(75)90006-9. PMID 772705. 11α Hydroxyprogesterone, while devoid of androgenic, estrogenic and progestational activity, is weakly anti androgenic in castrate rats.
  5. ^ Nguyen KT, Virus C, Günnewich N, Hannemann F, Bernhardt R (May 2012). "Changing the regioselectivity of a P450 from C15 to C11 hydroxylation of progesterone". ChemBioChem. 13 (8): 1161–1166. doi:10.1002/cbic.201100811. PMID 22532270. S2CID 34483686. 11α-Hydroxyprogesterone is an important pharmaceutical compound with anti-androgenic and blood-pressure-regulating activity. [...] 11α-Hydroxyprogesterone can therefore influence blood pressure regulation.12 Furthermore, 11α-hydroxyprogesterone exhibits an anti-androgenic activity with minimal estrogenic and progestational side effects.13 This substance has been proposed for treating skin diseases, especially for psoriasis in combination with clobetasol propionate and minoxidil.14.
  6. ^ Tindall DJ, Chang CH, Lobl TJ, Cunningham GR (1984). "Androgen antagonists in androgen target tissues". Pharmacology & Therapeutics. 24 (3): 367–400. doi:10.1016/0163-7258(84)90010-X. PMID 6205409.
  7. ^ Millikan LE (19 April 2016). Drug Therapy in Dermatology. CRC Press. p. 403. ISBN 978-0-203-90831-0. Topical antiandrogens have also been tried, including topical progesterone, which proved ineffective. However, small studies with topical 11α-hydroxyprogesterone and 17α-estradiol showed some benefit [38,39].
  8. ^ a b Morita H, Zhou M, Foecking MF, Gomez-Sanchez EP, Cozza EN, Gomez-Sanchez CE (June 1996). "11 beta-Hydroxysteroid dehydrogenase type 2 complementary deoxyribonucleic acid stably transfected into Chinese hamster ovary cells: specific inhibition by 11 alpha-hydroxyprogesterone". Endocrinology. 137 (6): 2308–2314. doi:10.1210/endo.137.6.8641180. PMID 8641180. 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM).
  9. ^ Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, et al. (October 2004). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocrine Reviews. 25 (5): 831–866. doi:10.1210/er.2003-0031. PMID 15466942. In intact cells 11α-hydroxyprogesterone is a more potent inhibitor of 11β-HSD1 than glycyrrhetinic acid or 11β-hydroxyprogesterone (117, 118).
  10. ^ Bujalska I, Shimojo M, Howie A, Stewart PM (January 1997). "Human 11 beta-hydroxysteroid dehydrogenase: studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue". Steroids. 62 (1): 77–82. doi:10.1016/S0039-128X(96)00163-8. PMID 9029719. S2CID 22551136.
  11. ^ Dunn PJ, Wells A, Williams MT (2 February 2010). Green Chemistry in the Pharmaceutical Industry. John Wiley & Sons. pp. 2–. ISBN 978-3-527-62969-5.
  12. ^ Lamberth C, Dinges J (17 May 2016). Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals. Wiley. pp. 250–. ISBN 978-3-527-69396-2.
  13. ^ Ramawat KG, Mérillon JM (16 October 2008). Bioactive Molecules and Medicinal Plants. Springer Science & Business Media. pp. 5–. ISBN 978-3-540-74603-4.
Stub icon

This article about a steroid is a stub. You can help Wikipedia by expanding it.

Stub icon

This dermatologic drug article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=11α-Hydroxyprogesterone&oldid=1226250672"