Human Metabolome Database Version 3.5

Showing metabocard for 17-Hydroxyprogesterone (HMDB00374)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:08:26 -0700
HMDB ID HMDB00374
Secondary Accession Numbers None
Metabolite Identification
Common Name 17-Hydroxyprogesterone
Description It serves as an intermediate in the biosynthesis of hydrocortisone and gonadal steroid hormones. It is derived from progesterone via 17-hydroxylase, a P450c17 enzyme, or from 17-hydroxypregnenolone via 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase. 17-Hydroxyprogesterone is a natural progestin and in pregnancy increases in the third trimester primarily due to fetal adrenal production. This hormone is primarily produced in the adrenal glands and to some degree in the gonads, specifically the corpus luteum of the ovary. Normal levels are 3-90 ng/dl in children, and in women, 15-70 ng/dl prior to ovulation, and 35-290 ng/dl during the luteal phase. Measurements of levels of 17-hydroxyprogesterone are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17OHP. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17OHP. 17OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but not 17OHP is also contributed by the placenta.
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. 17-alpha-Hydroxyprogesterone
  2. 17-Hydroxypregn-4-ene-3,20-dione
  3. 17-Hydroxyprogesterone
  4. 17-OH Progesterone
  5. 17-OHP
  6. 17a-Hydroxypregn-4-ene-3,20-dione
  7. 17a-Hydroxyprogesterone
  8. 17alpha-hydroxyprogesterone
  9. D4-Pregnen-17a-ol-3,20-dione
  10. Gestageno
  11. Gestageno Gador
  12. Hydroxyprogesterone
  13. Pregn-4-en-17a-ol-3,20-dione
  14. Prodix
  15. Prodox
Chemical Formula C21H30O3
Average Molecular Weight 330.4611
Monoisotopic Molecular Weight 330.219494826
IUPAC Name (1S,2R,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
Traditional IUPAC Name hydroxyprogesterone
CAS Registry Number 68-96-2
SMILES [H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
InChI Identifier InChI=1S/C21H30O3/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/h12,16-18,24H,4-11H2,1-3H3/t16-,17+,18+,19+,20+,21+/m1/s1
InChI Key DBPWSSGDRRHUNT-CEGNMAFCSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Lipids
Class Steroids and Steroid Derivatives
Sub Class Gluco/mineralocorticoids, Progestogins and Derivatives
Other Descriptors
  • 17alpha-hydroxy steroid(ChEBI)
  • Aliphatic Homopolycyclic Compounds
  • C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives(Lipidmaps)
  • Progestagens(KEGG)
Substituents
  • 17 Hydroxy Steroid
  • 20 Keto Steroid
  • 3 Keto Steroid
  • Cyclic Alcohol
  • Cyclohexane
  • Cyclohexene
  • Decaline
  • Ketone
  • Tertiary Alcohol
Direct Parent Gluco/mineralocorticoids, Progestogins and Derivatives
Ontology
Status Detected 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
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 219 - 220 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 0.00648 mg/mL Not Available
LogP 3.17 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
Water Solubility 0.029 g/L ALOGPS
LogP 2.99 ALOGPS
LogP 3.4 ChemAxon
LogS -4.05 ALOGPS
pKa (strongest acidic) 12.7 ChemAxon
pKa (strongest basic) -3.8 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 54.37 A2 ChemAxon
Rotatable Bond Count 1 ChemAxon
Refractivity 94.11 ChemAxon
Polarizability 37.93 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum EI-B (HITACHI M-80)
MS/MS Spectrum GC-MS
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Testes
  • Adrenal Gland
  • Adipose Tissue
  • Adrenal Cortex
Pathways
Name SMPDB Link KEGG Link
Steroidogenesis SMP00130 map00140 Link_out
Androgen and Estrogen Metabolism SMP00068 map00150 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.011 (0.0003-0.023) uM Infant (0-1 year old) Both Normal
Blood Detected and Quantified
0.0014 (0.000030-0.0028) uM Adult (>18 years old) Both Normal
Saliva Detected and Quantified
<1.00 uM Adult (>18 years old) Both Normal
Urine Detected and Quantified
0.0013 +/- 0.00026 umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 0.152 (0.0022- 0.302) uM Adult (>18 years old) Both Phenylketonuria (PKU)
Blood Detected and Quantified 0.016 (0.0090-0.024) uM Children (1-13 year old) Both 21-Hydroxylase Deficiency (CYP21)
Urine Detected and Quantified 0.0017 +/- 0.00034 umol/mmol creatinine Adult (>18 years old) Both Comment Systemic lupus erythematosus (SLE)
Urine Detected and Quantified 0.00065 +/- 0.00011 umol/mmol creatinine Adult (>18 years old) Both Comment Rheumatoid arthritis
Urine Detected and Quantified 0.00077 +/- 0.0002 umol/mmol creatinine Adult (>18 years old) Both Comment Rheumatoid arthritis
Urine Detected and Quantified 0.0022 +/- 0.00058 umol/mmol creatinine Adult (>18 years old) Both Comment Systemic lupus erythematosus (SLE)
Associated Disorders and Diseases
Disease References
Phenylketonuria
  • Elvers LH, Loeber JG, Dhondt JL, Fukushi M, Hannon WH, Torresani T, Webster D: First ISNS Reference Preparation for Neonatal Screening for thyrotropin, phenylalanine and 17alpha-hydroxyprogesterone in blood spots. J Inherit Metab Dis. 2007 Aug;30(4):609. Epub 2007 Jun 14. Pubmed: 17574536 Link_out
      Rheumatoid arthritis
      • Straub RH, Weidler C, Demmel B, Herrmann M, Kees F, Schmidt M, Scholmerich J, Schedel J: Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 2004 Aug;63(8):961-8. Pubmed: 15249323 Link_out
          21-hydroxylase deficiency
              Associated OMIM IDs
              DrugBank ID Not Available
              DrugBank Metabolite ID Not Available
              Phenol Explorer Compound ID Not Available
              Phenol Explorer Metabolite ID Not Available
              FoodDB ID FDB021992
              KNApSAcK ID Not Available
              Chemspider ID 6002 Link_out
              KEGG Compound ID C01176 Link_out
              BioCyc ID Not Available
              BiGG ID 36989 Link_out
              Wikipedia Link 17-Hydroxyprogesterone Link_out
              NuGOwiki Link HMDB00374 Link_out
              Metagene Link HMDB00374 Link_out
              METLIN ID 5363 Link_out
              PubChem Compound 6238 Link_out
              PDB ID 3QZ Link_out
              ChEBI ID 17252 Link_out
              References
              Synthesis Reference Schneider, Carlos; Silva, Mario; Zunza, Hilda; Becerra, Jose. Synthesis of 17.alpha.-hydroxyprogesterone from androstenedione. Boletin de la Sociedad Chilena de Quimica (1999), 44(2), 167-172.
              Material Safety Data Sheet (MSDS) Download (PDF)
              General References
              1. Sahin Y, Kelestimur F: 17-Hydroxyprogesterone responses to gonadotrophin-releasing hormone agonist buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of adrenal and ovarian cytochrome P450c17alpha dysregulation. Hum Reprod. 1997 May;12(5):910-3. Pubmed: 9194638 Link_out
              2. Kirchengast S, Hartmann B, Huber J: Serum levels of sex hormones, thyroid hormones, growth hormone, IGF I, and cortisol and their relations to body fat distribution in healthy women dependent on their menopausal status. Z Morphol Anthropol. 1996 Sep;81(2):223-34. Pubmed: 9270338 Link_out
              3. Hampl R, Lachman M, Novak Z, Sulcova J, Starka L: Serum levels of steroid hormones in men with varicocele and oligospermia as compared to normozoospermic men. Exp Clin Endocrinol. 1992;100(3):117-9. Pubmed: 1305061 Link_out
              4. Gibney MJ, Walsh M, Brennan L, Roche HM, German B, van Ommen B: Metabolomics in human nutrition: opportunities and challenges. Am J Clin Nutr. 2005 Sep;82(3):497-503. Pubmed: 16155259 Link_out
              5. White PC, Tusie-Luna MT, New MI, Speiser PW: Mutations in steroid 21-hydroxylase (CYP21). Hum Mutat. 1994;3(4):373-8. Pubmed: 8081391 Link_out
              6. Ibanez L, de Zegher F, Potau N: Anovulation after precocious pubarche: early markers and time course in adolescence. J Clin Endocrinol Metab. 1999 Aug;84(8):2691-5. Pubmed: 10443661 Link_out
              7. Katagiri M, Kagawa N, Waterman MR: The role of cytochrome b5 in the biosynthesis of androgens by human P450c17. Arch Biochem Biophys. 1995 Mar 10;317(2):343-7. Pubmed: 7893148 Link_out
              8. al Saedi S, Dean H, Dent W, Cronin C: Reference ranges for serum cortisol and 17-hydroxyprogesterone levels in preterm infants. J Pediatr. 1995 Jun;126(6):985-7. Pubmed: 7776113 Link_out
              9. Gupta MK, Guryev OL, Auchus RJ: 5alpha-reduced C21 steroids are substrates for human cytochrome P450c17. Arch Biochem Biophys. 2003 Oct 15;418(2):151-60. Pubmed: 14522586 Link_out
              10. Escobar-Morreale HF, San Millan JL, Smith RR, Sancho J, Witchel SF: The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations. Fertil Steril. 1999 Oct;72(4):629-38. Pubmed: 10521100 Link_out
              11. Wilson SC, Hodgins MB, Scott JS: Incomplete masculinization due to a deficiency of 17 beta-hydroxysteroid dehydrogenase: comparison of prepubertal and peripubertal siblings. Clin Endocrinol (Oxf). 1987 Apr;26(4):459-69. Pubmed: 2820622 Link_out
              12. Toscano V, Sancesario G, Bianchi P, Cicardi C, Casilli D, Giacomini P: Cerebrospinal fluid estrone in pseudotumor cerebri: a change in cerebral steroid hormone metabolism? J Endocrinol Invest. 1991 Feb;14(2):81-6. Pubmed: 2061573 Link_out
              13. Mellon SH, Miller WL: Extraadrenal steroid 21-hydroxylation is not mediated by P450c21. J Clin Invest. 1989 Nov;84(5):1497-502. Pubmed: 2808702 Link_out
              14. Shackleton C, Malunowicz E: Apparent pregnene hydroxylation deficiency (APHD): seeking the parentage of an orphan metabolome. Steroids. 2003 Oct;68(9):707-17. Pubmed: 14625002 Link_out
              15. Bolt RJ, Van Weissenbruch MM, Popp-Snijders C, Sweep FG, Lafeber HN, Delemarre-van de Waal HA: Maturity of the adrenal cortex in very preterm infants is related to gestational age. Pediatr Res. 2002 Sep;52(3):405-10. Pubmed: 12193676 Link_out

              Enzymes
              Name: Aldo-keto reductase family 1 member C1
              Reactions:
              17-alpha,20-alpha-Dihydroxypregn-4-en-3-one + NAD(P)(+) unknown 17-Hydroxyprogesterone + NAD(P)H details
              Gene Name: AKR1C1
              Uniprot ID: Q04828 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Cytochrome P450 11B1, mitochondrial
              Reactions:
              17-Hydroxyprogesterone + Reduced ferredoxin + Oxygen unknown 21-Deoxycortisol + Oxidized ferredoxin + Water details
              Gene Name: CYP11B1
              Uniprot ID: P15538 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Steroid 17-alpha-hydroxylase/17,20 lyase
              Reactions:
              Progesterone + Reduced acceptor + Oxygen unknown 17-Hydroxyprogesterone + Acceptor + Water details
              17-Hydroxyprogesterone + Reduced acceptor + Oxygen unknown Androstenedione + Acetic acid + Acceptor + Water details
              Gene Name: CYP17A1
              Uniprot ID: P05093 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1
              Reactions:
              17a-Hydroxypregnenolone + NAD unknown 17-Hydroxyprogesterone + NADH + Hydrogen Ion details
              Gene Name: HSD3B1
              Uniprot ID: P14060 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2
              Reactions:
              17a-Hydroxypregnenolone + NAD unknown 17-Hydroxyprogesterone + NADH + Hydrogen Ion details
              Gene Name: HSD3B2
              Uniprot ID: P26439 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Cytochrome P450 11B2, mitochondrial
              Reactions:
              17-Hydroxyprogesterone + Reduced ferredoxin + Oxygen unknown 21-Deoxycortisol + Oxidized ferredoxin + Water details
              Gene Name: CYP11B2
              Uniprot ID: P19099 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Cytochrome P450, family 21, subfamily A, polypeptide 2
              Reactions: Not Available
              Gene Name: CYP21A2
              Uniprot ID: Q08AG9 Link_out
              Protein Sequence: FASTA
              Gene Sequence: FASTA
              Name: Steroid 21-hydroxylase
              Reactions:
              17-Hydroxyprogesterone + Reduced acceptor + Oxygen unknown Cortexolone + Acceptor + Water details
              Gene Name: CYP21A2
              Uniprot ID: P08686 Link_out
              Protein Sequence: FASTA