11α-Hydroxyprogesterone

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

References

  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.
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