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Record Information
Version3.6
Creation Date2006-08-13 09:23:58 UTC
Update Date2013-05-29 19:39:23 UTC
HMDB IDHMDB04031
Secondary Accession Numbers
  • HMDB13594
Metabolite Identification
Common Name11b-Hydroxyprogesterone
Description11beta-Hydroxyprogesterone is a normal human metabolite. Plasma 11beta-Hydroxyprogesterone concentrations does not vary significantly as a function of age, sex, or phase of the menstrual cycle, in contrast to 17-hydroxyprogesterone. Increased plasma 11beta-Hydroxyprogesterone levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway. 21-hydroxylase deficiency (OMIM 201910 ) is probably the most frequent (if not the most frequent) autosomal recessive genetic disease, occurring in almost 1% of Caucasians and about 3% of Ashkenazi Jews. 21-hydroxylase deficiency is unusual among genetic diseases in that approximately 95% of the mutant alleles have apparently been generated by recombination between a normally active gene (CYP21) and a closely linked pseudogene (CYP21P). There are 4 recognized clinical forms of congenital adrenal hyperplasia, the majority of cases being associated with 21-hydroxylase deficiency: salt-wasting (SW), simple virilizing (SV), nonclassic (NC) late-onset (also called attenuated and acquired), and cryptic. (PMID: 3546944 , 2537337 ). 11beta-hydroxyprogesterone acts as a mineralocorticoid agonist in stimulating Na+ absorption in mammalian principal cortical collecting duct cells.It activates the transiently expressed hMR in COS-7 cells in a dose-dependent manner (ED(50): 10(-8) M) and, like aldosterone, stimulated Ams I(sc) in mpkCCD(cl4) cells. Docking 11OHP within the hMR-ligand-binding domain homology model revealed that the agonist activity of 11OHP is caused by contacts between its 11 beta-hydroxyl group and Asn770. Furthermore, 11OHP was unable to activate the mutant hMR/N770A, in which Ala is substituted for Asn at position 770. These findings demonstrate that in the absence of the 21-hydroxyl group, the 11 beta-hydroxyl group can produce the contact with the hMR-Asn770 required for the hMR activation leading to stimulated Na(+) absorption.
Structure
Thumb
Synonyms
  1. (11beta)-11-hydroxypregn-4-ene-3,20-dione
  2. 11-beta-Hydroxypregn-4-ene-3,20-dione
  3. 11-beta-Hydroxyprogesterone
  4. 11b-Hydroxyprogesterone
  5. 11beta-hydroxypregn-4-ene-3,20-dione
  6. 11beta-Hydroxyprogesterone
  7. 21-Deoxycorticosterone
Chemical FormulaC20H28O4
Average Molecular Weight332.4339
Monoisotopic Molecular Weight332.198759384
IUPAC Name(1S,2R,10S,11S,14S,15S,17R)-17-hydroxy-2,15-dimethyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-14-carboxylic acid
Traditional Name11β-hydroxyprogesterone
CAS Registry Number600-57-7
SMILES
[H][C@@]12CC[C@H](C(O)=O)[C@@]1(C)C[C@@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
InChI Identifier
InChI=1S/C20H28O4/c1-19-8-7-12(21)9-11(19)3-4-13-14-5-6-15(18(23)24)20(14,2)10-16(22)17(13)19/h9,13-17,22H,3-8,10H2,1-2H3,(H,23,24)/t13-,14-,15+,16+,17+,19-,20-/m0/s1
InChI KeyXEFVQCSDIKHROY-CAPFDLLWSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassLipids
ClassSteroids and Steroid Derivatives
Sub ClassGluco/mineralocorticoids, Progestogins and Derivatives
Other Descriptors
  • Aliphatic Homopolycyclic Compounds
  • C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives(Lipidmaps)
Substituents
  • 11 Hydroxy Steroid
  • 3 Keto Steroid
  • Carboxylic Acid
  • Cyclic Alcohol
  • Cyclohexane
  • Cyclohexene
  • Decaline
  • Ketone
  • Secondary Alcohol
Direct ParentGluco/mineralocorticoids, Progestogins and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.064ALOGPS
logP1.97ALOGPS
logP2.51ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)4.68ChemAxon
pKa (Strongest Basic)-0.26ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity90.75 m3·mol-1ChemAxon
Polarizability36.77 Å3ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Bladder
  • Epidermis
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Muscle
  • Myelin
  • Nerve Cells
  • Neuron
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Testes
  • Thyroid Gland
Pathways
NameSMPDB LinkKEGG Link
SteroidogenesisSMP00130map00140
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00002 +/- 0.00001 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023284
KNApSAcK IDNot Available
Chemspider ID24840621
KEGG Compound IDC05498
BioCyc IDCPD-272
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB04031
Metagene LinkHMDB04031
METLIN ID7005
PubChem Compound44263342
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceRosenkranz, G.; Pataki, J.; Djerassi, Carl. Steroids. XXIX. Synthesis of 11b-hydroxyprogesterone. Journal of Organic Chemistry (1952), 17 290-3.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Holtta-Vuori M, Maatta J, Ullrich O, Kuismanen E, Ikonen E: Mobilization of late-endosomal cholesterol is inhibited by Rab guanine nucleotide dissociation inhibitor. Curr Biol. 2000 Jan 27;10(2):95-8. Pubmed: 10662671
  2. Herrero P, Soto PF, Dence CS, Kisrieva-Ware Z, Delano DA, Peterson LR, Gropler RJ: Impact of hormone replacement on myocardial fatty acid metabolism: potential role of estrogen. J Nucl Cardiol. 2005 Sep-Oct;12(5):574-81. Pubmed: 16171718
  3. Laatikainen T, Apter D, Wahlstrom T: Steroids in spermatic and peripheral vein blood in testicular feminization. Fertil Steril. 1980 Nov;34(5):461-4. Pubmed: 7439411
  4. Tuckey RC: Progesterone synthesis by the human placenta. Placenta. 2005 Apr;26(4):273-81. Pubmed: 15823613
  5. Lambert JJ, Belelli D, Peden DR, Vardy AW, Peters JA: Neurosteroid modulation of GABAA receptors. Prog Neurobiol. 2003 Sep;71(1):67-80. Pubmed: 14611869
  6. Antic T, Perry KT, Harrison K, Zaytsev P, Pins M, Campbell SC, Picken MM: Mixed epithelial and stromal tumor of the kidney and cystic nephroma share overlapping features: reappraisal of 15 lesions. Arch Pathol Lab Med. 2006 Jan;130(1):80-5. Pubmed: 16390243
  7. Shikone T, Matzuk MM, Perlas E, Finegold MJ, Lewis KA, Vale W, Bradley A, Hsueh AJ: Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor. Mol Endocrinol. 1994 Aug;8(8):983-95. Pubmed: 7997239
  8. Barnhill SD, Zhang Z, Madyastha KR: Evaluation of a new biochemical index for the estimation of bone demineralization using artificial intelligence. Contemp Orthop. 1995 Apr;30(4):315-8. Pubmed: 10150355
  9. Saxena BB, Clavio A, Singh M, Rathnam P, Bukharovich EY, Reimers TJ Jr, Saxena A, Perkins S: Effect of immunization with bovine luteinizing hormone receptor on ovarian function in cats. Am J Vet Res. 2003 Mar;64(3):292-8. Pubmed: 12661868
  10. Wiebe JP: Nongenomic actions of steroids on gonadotropin release. Recent Prog Horm Res. 1997;52:71-99; discussion 99-101. Pubmed: 9238848
  11. Celayir S, Ilce Z, Dervisoglu S: The sex hormone receptors in the bladder in childhood - I: preliminary report in male subjects. Eur J Pediatr Surg. 2002 Oct;12(5):312-7. Pubmed: 12469257
  12. Agoulnik IU, Krause WC, Bingman WE 3rd, Rahman HT, Amrikachi M, Ayala GE, Weigel NL: Repressors of androgen and progesterone receptor action. J Biol Chem. 2003 Aug 15;278(33):31136-48. Epub 2003 May 27. Pubmed: 12771131
  13. Beer R, Barnhill SD, Madyastha KR: Comparative study of a biochemical index for the estimation of bone demineralization and dual photon absorptiometry. Contemp Orthop. 1995 Mar;30(3):230-4. Pubmed: 10150317
  14. Pepe GJ, Albrecht ED: Actions of placental and fetal adrenal steroid hormones in primate pregnancy. Endocr Rev. 1995 Oct;16(5):608-48. Pubmed: 8529574
  15. Feuring M, Christ M, Roell A, Schueller P, Losel R, Dempfle CE, Schultz A, Wehling M: Alterations in platelet function during the ovarian cycle. Blood Coagul Fibrinolysis. 2002 Jul;13(5):443-7. Pubmed: 12138372
  16. Rasmussen KM, Kjolhede CL: Prepregnant overweight and obesity diminish the prolactin response to suckling in the first week postpartum. Pediatrics. 2004 May;113(5):e465-71. Pubmed: 15121990
  17. Parikh P, Chan TY, Epstein JI, Argani P: Incidental stromal-predominant mixed epithelial-stromal tumors of the kidney: a mimic of intraparenchymal renal leiomyoma. Arch Pathol Lab Med. 2005 Jul;129(7):910-4. Pubmed: 15974815
  18. Money SR, Muss W, Thelmo WL, Boeckl O, Pimpl W, Kaindl H, Sungler P, Kirwin J, Waclawicek H, Jaffe BM, et al.: Immunocytochemical localization of estrogen and progesterone receptors in human thyroid. Surgery. 1989 Dec;106(6):975-8; discussion 979. Pubmed: 2686061
  19. Karalis K, Goodwin G, Majzoub JA: Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor. Nat Med. 1996 May;2(5):556-60. Pubmed: 8616715
  20. Sereda MW, Meyer zu Horste G, Suter U, Uzma N, Nave KA: Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat Med. 2003 Dec;9(12):1533-7. Epub 2003 Nov 9. Pubmed: 14608378
  21. Fiet J, Gueux B, Raux-DeMay MC, Kuttenn F, Vexiau P, Brerault JL, Couillin P, Galons H, Villette JM, Julien R, et al.: Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway. J Clin Endocrinol Metab. 1989 Mar;68(3):542-7. Pubmed: 2537337
  22. Gueux B, Fiet J, Galons H, Bonete R, Villette JM, Vexiau P, Pham-Huu-Trung MT, Raux-Eurin MC, Gourmelen M, Brerault JL, et al.: The measurement of 11 beta-hydroxy-4-pregnene-3,20-dione (21-deoxycorticosterone) by radioimmunoassay in human plasma. J Steroid Biochem. 1987 Jan;26(1):145-50. Pubmed: 3546944

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
Gene Name:
CYP11B1
Uniprot ID:
P15538
Molecular weight:
57572.44
Reactions
Progesterone + Reduced ferredoxin + Oxygen → 11b-Hydroxyprogesterone + Oxidized ferredoxin + Waterdetails
General function:
Involved in monooxygenase activity
Specific function:
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.
Gene Name:
CYP17A1
Uniprot ID:
P05093
Molecular weight:
57369.995
Reactions
21-Deoxycortisol + Acceptor + Water → 11b-Hydroxyprogesterone + Reduced acceptor + Oxygendetails
General function:
Involved in monooxygenase activity
Specific function:
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name:
CYP11B2
Uniprot ID:
P19099
Molecular weight:
57559.62
Reactions
Progesterone + Reduced ferredoxin + Oxygen → 11b-Hydroxyprogesterone + Oxidized ferredoxin + Waterdetails
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP21A2
Uniprot ID:
Q08AG9
Molecular weight:
55972.9
General function:
Not Available
Specific function:
Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Gene Name:
CYP21A2
Uniprot ID:
P08686
Molecular weight:
56000.94
Reactions
11b-Hydroxyprogesterone + Reduced acceptor + Oxygen → Corticosterone + Acceptor + Waterdetails