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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2018-05-20 08:51:51 UTC
HMDB IDHMDB0000363
Secondary Accession Numbers
  • HMDB00363
Metabolite Identification
Common Name17a-Hydroxypregnenolone
Description17a-Hydroxypregnenolone is a 21-carbon steroid that is converted from pregnenolone by cytochrome P450 17alpha hydroxylase/C17,20 lyase (CYP17, EC 1.14.99.9). 17a-Hydroxypregnenolone is an intermediate in the delta-5 pathway of biosynthesis of gonadal steroid hormones and the adrenal corticosteroids. The first, rate-limiting and hormonally regulated step in the biosynthesis of all steroid hormones is the conversion of cholesterol to pregnenolone. The conversion of cholesterol to pregnenolone is accomplished by the cleavage of the cholesterol side chain, catalyzed by a mitochondrial cytochrome P450 enzyme termed P450scc where scc designates Side Chain Cleavage. All steroid hormones are made from the pregnenolone produced by P450scc; thus, the presence or absence of each of the activities of CYP17 directs this pregnenolone towards its final metabolic pathway. While all cytochrome P450 enzymes can catalyze multiple reactions on a single active site, CYP17 is the only one described to date in which these multiple activities are differentially regulated by a physiologic process. 17a-Hydroxypregnenolone is converted to dehydroepiandrosterone by the 17,20 lyase activity of CYP17. The ratio of the 17,20 lyase to 17 alpha-hydroxylase activity of CYP17 determines the ratio of C21 to C19 steroids produced. This ratio is regulated post-translationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase, the presence of cytochrome b5, and the serine phosphorylation of CYP17. (PMID: 12573809 ).
Structure
Thumb
Synonyms
ValueSource
(3beta)-3,17-Dihydroxypregn-5-en-20-oneChEBI
17-HydroxypregnenoloneChEBI
5-Pregnen-3beta,17alpha-diol-20-oneChEBI
(3b)-3,17-Dihydroxypregn-5-en-20-oneGenerator
(3β)-3,17-dihydroxypregn-5-en-20-oneGenerator
5-Pregnen-3b,17a-diol-20-oneGenerator
5-Pregnen-3β,17α-diol-20-oneGenerator
17-Hydroxy-D5-pregnenoloneHMDB
17-OH-PregnenoloneHMDB
17a-HydroxypregnoloneHMDB
17alpha-HydroxypregnanoloneHMDB
17alpha-HydroxypregnenoloneHMDB
3b,17-Dihydroxy-5-pregnen-20-oneHMDB
3b,17-Dihydroxy-pregn-5-en-20-oneHMDB
3b,17a-Dihydroxypregn-5-en-20-oneHMDB
17alpha HydroxypregnenoloneMeSH
HydroxypregnenoloneMeSH
17 HydroxypregnenoloneMeSH
17 alpha HydroxypregnenoloneMeSH
17-Hydroxypregnenolone, (3alpha)-isomerMeSH
17-Hydroxypregnenolone, (3beta,13alpha)-isomerMeSH
17-alpha-HydroxypregnenoloneMeSH
17 alpha-HydroxypregnenoloneMeSH
17-Hydroxypregnenolone, (3beta,13alpha,17alpha)-isomerMeSH
17-Hydroxypregnenolone, (3beta,17alpha)-isomerMeSH
Chemical FormulaC21H32O3
Average Molecular Weight332.477
Monoisotopic Molecular Weight332.23514489
IUPAC Name1-[(1S,2R,5S,10R,11S,14R,15S)-5,14-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-14-yl]ethan-1-one
Traditional Name17-hydroxypregnenolone
CAS Registry Number387-79-1
SMILES
[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C
InChI Identifier
InChI=1S/C21H32O3/c1-13(22)21(24)11-8-18-16-5-4-14-12-15(23)6-9-19(14,2)17(16)7-10-20(18,21)3/h4,15-18,23-24H,5-12H2,1-3H3/t15-,16+,17-,18-,19-,20-,21-/m0/s1
InChI KeyJERGUCIJOXJXHF-TVWVXWENSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • 20-oxosteroid
  • 3-hydroxy-delta-5-steroid
  • 3-hydroxysteroid
  • 17-hydroxysteroid
  • 3-beta-hydroxysteroid
  • 3-beta-hydroxy-delta-5-steroid
  • Oxosteroid
  • Hydroxysteroid
  • Delta-5-steroid
  • Alpha-hydroxy ketone
  • Tertiary alcohol
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Organic oxygen compound
  • Organooxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxide
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point266 - 271 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.038 g/LALOGPS
logP3.15ALOGPS
logP2.83ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)12.7ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity95.16 m³·mol⁻¹ChemAxon
Polarizability38.75 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-054x-4900000000-df86d10979d808f20e67View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-0a73-3910000000-7a0eea991ac4d2fac97eView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0f89-2891000000-3605ad7dd57f97382115View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ff0-3792000000-974e157d4c25e376b004View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-054x-4900000000-df86d10979d808f20e67View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0a73-3910000000-7a0eea991ac4d2fac97eView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000f-3295000000-48ed11374901b134a70dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-03di-0111900000-e55e71b4d8c63cde89c2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-001i-0039000000-28c103ca6cdf072557bfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-0900000000-ae3004bb674d9632cd0cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-014i-0900000000-a2f467560b451d5c9b0eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-52) , Positivesplash10-0f89-2891000000-82e62584fff36943bcbaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0159-0029000000-131b75950fb7123106d9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-015i-0094000000-2a48017855d3965d5626View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0g29-2690000000-3d1b2b0525a2f6da149cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-4c286aa6d88850e66ba9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-008i-0098000000-77ce542de402b225ac27View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0avr-0092000000-e39f57cc01b46a017728View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
Tissue Locations
  • Adrenal Cortex
  • Testes
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00180-0.00451 uMNewborn (0-30 days old)Female
Normal
details
BloodDetected and Quantified0.00211-0.0256 uMNewborn (0-30 days old)Female
Normal
details
BloodDetected and Quantified0.00902 +/- 0.00361 uMAdult (>18 years old)Female
Normal
details
BloodDetected and Quantified0.000300-0.0240 uMInfant (0-1 year old)Not SpecifiedNormal details
BloodDetected and Quantified0.000782 +/- 0.000993 uMChildren (1-13 years old)Both
Normal
details
BloodDetected and Quantified0.00656 +/- 0.00562 uMChildren (1-13 years old)Both
Normal
details
BloodDetected and Quantified0.003 (0.000 - 0.006) uMAdult (>18 years old)FemaleNormal details
BloodDetected and Quantified0.006 (0.001-0.012) uMAdult (>18 years old)MaleNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000271 uMNewborn (0-30 days old)Female
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
details
BloodDetected and Quantified0.00123 uMNewborn (0-30 days old)Female
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
details
BloodDetected and Quantified0.0126 +/- 0.0105 uMNewborn (0-30 days old)Not Specified
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.00440 +/- 0.00280 uMChildren (1-13 years old)Not Specified
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.159 uMAdult (>18 years old)Male
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.741 uMAdolescent (13-18 years old)Male
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.0264-0.103 uMChildren (1-13 years old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.0843-1.262 uMNewborn (0-30 days old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.00230 +/- 0.00200 uMChildren (1-13 years old)BothAdrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency details
BloodDetected and Quantified0.00300 +/- 0.00250 uMAdult (>18 years old)FemaleAdrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency details
BloodDetected and Quantified0.00380 +/- 0.00210 uMAdult (>18 years old)MaleAdrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency details
BloodDetected and Quantified0.00896 +/- 0.00770 uMInfant (0-1 year old)Not SpecifiedAdrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency details
BloodDetected and Quantified0.0186 uMAdult (>18 years old)Female
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.0120-0.180 uMInfant (0-1 year old)Both
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
details
BloodDetected and Quantified0.136 +/- 0.129 uMChildren (1-13 years old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.00439 +/- 0.00896 uMChildren (1-13 years old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.176 +/- 0.186 uMChildren (1-13 years old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
BloodDetected and Quantified0.0111 +/- 0.0219 uMChildren (1-13 years old)Both
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
details
Associated Disorders and Diseases
Disease References
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency
  1. Hattori N, Ishihara T, Moridera K, Hino M, Ikekubo K, Kurahachi H: A case of late-onset congenital adrenal hyperplasia due to partial 3 beta-hydroxysteroid dehydrogenase deficiency. Endocr J. 1993 Feb;40(1):107-9. [PubMed:7951484 ]
  2. Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S: Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 2002 Jun;87(6):2611-22. doi: 10.1210/jcem.87.6.8615. [PubMed:12050224 ]
  3. Benkert AR, Young M, Robinson D, Hendrickson C, Lee PA, Strauss KA: Severe Salt-Losing 3beta-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes. J Clin Endocrinol Metab. 2015 Aug;100(8):E1105-15. doi: 10.1210/jc.2015-2098. Epub 2015 Jun 16. [PubMed:26079780 ]
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete
  1. Kim CJ, Lin L, Huang N, Quigley CA, AvRuskin TW, Achermann JC, Miller WL: Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc. J Clin Endocrinol Metab. 2008 Mar;93(3):696-702. doi: 10.1210/jc.2007-2330. Epub 2008 Jan 8. [PubMed:18182448 ]
Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis
  1. Fukami M, Hasegawa T, Horikawa R, Ohashi T, Nishimura G, Homma K, Ogata T: Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and/or aromatase deficiency: diagnostic value of urine steroid hormone analysis. Pediatr Res. 2006 Feb;59(2):276-80. doi: 10.1203/01.pdr.0000195825.31504.28. [PubMed:16439592 ]
Associated OMIM IDs
  • 201810 (Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency)
  • 201750 (Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis)
  • 613743 (Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB021982
KNApSAcK IDNot Available
Chemspider ID82579
KEGG Compound IDC05138
BioCyc IDCPD66-23
BiGG ID45199
Wikipedia Link17-Hydroxypregnenolone
METLIN ID5352
PubChem Compound91451
PDB IDLZZ
ChEBI ID28750
References
Synthesis ReferenceKaspar, Emanuel; Hiersemann, Wolfgang; Schenck, Martin. Preparation from their esters of steroid alcohols that are sensitive to acids and alkali. (1958), DE 1028572 19580424 CAN 54:74845 AN 1960:74845 CAPLUS
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Shimozawa K, Saisho S, Yata J, Kambegawa A: Age-related changes in serum 17-hydroxypregnenolone and 17-hydroxypregnenolone sulfate concentrations in human infancy and childhood. Endocrinol Jpn. 1988 Apr;35(2):189-95. [PubMed:3208699 ]
  2. Rodriguez-Rigau LJ, Weiss DB, Smith KD, Steinberger E: Suggestion of abnormal testicular steroidogenesis in some oligospermic men. Acta Endocrinol (Copenh). 1978 Feb;87(2):400-12. [PubMed:580138 ]
  3. Kaufman FR, Costin G, Goebelsmann U, Stanczyk FZ, Zachmann M: Male pseudohermaphroditism due to 17,20-desmolase deficiency. J Clin Endocrinol Metab. 1983 Jul;57(1):32-6. [PubMed:6853680 ]
  4. Miller WL: Androgen biosynthesis from cholesterol to DHEA. Mol Cell Endocrinol. 2002 Dec 30;198(1-2):7-14. [PubMed:12573809 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name:
CYP11A1
Uniprot ID:
P05108
Molecular weight:
60101.87
Reactions
17a,20a-Dihydroxycholesterol + Oxygen + Hydrogen Ion + Reduced adrenal ferredoxin → 17a-Hydroxypregnenolone + 4-Methylpentanal + Water + Oxidized adrenal ferredoxindetails
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
Pregnenolone + Reduced acceptor + Oxygen → 17a-Hydroxypregnenolone + Acceptor + Waterdetails
17a-Hydroxypregnenolone + Reduced acceptor + Oxygen → Dehydroepiandrosterone + Acetic acid + Acceptor + Waterdetails
General function:
Involved in 3-beta-hydroxy-delta5-steroid dehydrogenase activity
Specific function:
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. Efficiently catalyzes the transformation of pregnenolone to progesterone, 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone, DHEA to 4-androstenedione, dihydrotestosterone to 5-alpha-androstane-3 beta,17 beta-diol, dehydroepiandrosterone to androstenedione and 5-alpha-androstan-3 beta,17 beta-diol to 5-alpha-dihydrotestosterone.
Gene Name:
HSD3B1
Uniprot ID:
P14060
Molecular weight:
42251.25
Reactions
17a-Hydroxypregnenolone + NAD → 17-Hydroxyprogesterone + NADH + Hydrogen Iondetails
General function:
Involved in 3-beta-hydroxy-delta5-steroid dehydrogenase activity
Specific function:
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.
Gene Name:
HSD3B2
Uniprot ID:
P26439
Molecular weight:
42051.845
Reactions
17a-Hydroxypregnenolone + NAD → 17-Hydroxyprogesterone + NADH + Hydrogen Iondetails
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
P450-CYP21B
Uniprot ID:
Q16874
Molecular weight:
56000.9
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
17a-Hydroxypregnenolone + NADPH + Hydrogen Ion + Oxygen → 17alpha,21-Dihydroxypregnenolone + NADP + Waterdetails