Banner
targets (5) enzymes (2)
for drugs
Identification
Name Dehydroepiandrosterone
Accession Number DB01708 (DB06593, EXPT00519)
Type small molecule
Groups nutraceutical
Description

Dehydroepiandrosterone (DHEA) is a major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (DHEA) can be converted to testosterone; androstenedione; estradiol; and estrone. Most of DHEA is sulfated (dehydroepiandrosterone sulfate) before secretion.

In the United States, DHEA or DHEAS have been advertised with claims that they may be beneficial for a wide variety of ailments. DHEA and DHEAS are readily available in the United States, where they are marketed as over-the-counter dietary supplements.

In Canada, a prescription is required to buy DHEA.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
3-beta-Hydroxy-5-androsten-17-one
5-Dehydroepiandrosterone
5-DHEA
DHA
DHEA
Prasterone
Salts Not Available
Brand names
Name Company
Fidelin Paladin
OVIGYN-D Alembic Pharmaceuicals Ltd
Brand mixtures Not Available
Categories
  • Adjuvants, Immunologic
CAS number 53-43-0
Weight Average: 288.4244
Monoisotopic: 288.20893014
Chemical Formula C19H28O2
InChI Key InChIKey=FMGSKLZLMKYGDP-USOAJAOKSA-N
InChI
InChI=1S/C19H28O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h3,13-16,20H,4-11H2,1-2H3/t13-,14-,15-,16-,18-,19-/m0/s1
Plain Text
IUPAC Name
(1S,2R,5S,10R,11S,15S)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-14-one
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@]([H])(O)CC[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication DHEA is taken as a supplement for a variety of unsubstantiated indications. The following indications have shown promise and are backed up by some scientific evidence: schizophrenia (DHEA may be more effective in women than men); improving the appearance of older people’s skin (taking DHEA by mouth seems to increase skin thickness and moisture, and decrease facial “age spots” in elderly men and women); improving ability to achieve an erection in men with sexual dysfunction. Additionally, DHEA has shown promise in improving symptoms of lupus (SLE). Taking DHEA by mouth along with conventional treatment may help reduce the number of times symptoms flare up and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids). DHEA also shows promise in the treatment of osteoporosis. Taking DHEA by mouth daily seems to improve bone mineral density (BMD) in older women and men with osteoporosis or osteopenia (pre-osteoporosis). DHEA may also increase BMD in young women with the eating disorder called anorexia nervosa. DHEA is often prescribed in India for the induction of ovulation to improve chances of pregnancy.
Pharmacodynamics DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. Regular exercise is known to increase DHEA production in the body. Calorie restriction has also been shown to increase DHEA in primates. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.
Mechanism of action DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.
Absorption Following a 50-mg DHEA PO dose in cynomolgus monkeys, systemic availability was only 3.1 +/- 0.4%. [PMID: 12970301]
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic. As shown by their high conversion ratios (in a study involving cynomolgus monkeys), the major circulating metabolites of DHEA are DHEA-S, androsterone glucuronide, and androstane-3 alpha,17 beta-diol-glucuronide. [PMID: 12970301]
Route of elimination Not Available
Half life 12 hours
Clearance Not Available
Toxicity Acute oral toxicity (LD50): >10000 mg/kg [Rat]. Lowest Published Toxic Dose (TDL) [Man] - Route: Oral; Dose: 10 mg/kg/2W intermittent.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Capsule Oral 25mg
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 140-141 °C PhysProp
water solubility 63.5 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 3.23 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 4.38e-02 g/l ALOGPS
logP 3.53 ALOGPS
logP 3.36 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 18.2 ChemAxon
pKa (strongest basic) -1.4 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 37.3 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 84.66 ChemAxon
polarizability 34.09 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. The NIH National Library of Medicine
  2. Baker WL, Karan S, Kenny AM: Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review. J Am Geriatr Soc. 2011 Jun;59(6):997-1002. doi: 10.1111/j.1532-5415.2011.03410.×. Epub 2011 Jun 7. Pubmed
  3. Alkatib AA, Cosma M, Elamin MB, Erickson D, Swiglo BA, Erwin PJ, Montori VM: A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009 Oct;94(10):3676-81. Epub 2009 Sep 22. Pubmed
  4. Arlt W: Dehydroepiandrosterone and ageing. Best Pract Res Clin Endocrinol Metab. 2004 Sep;18(3):363-80. Pubmed
  5. Wallace MB, Lim J, Cutler A, Bucci L: Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc. 1999 Dec;31(12):1788-92. Pubmed
  6. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK: Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006221. Pubmed
  7. Fuller SJ, Tan RS, Martins RN: Androgens in the etiology of Alzheimer’s disease in aging men and possible therapeutic interventions. J Alzheimers Dis. 2007 Sep;12(2):129-42. Pubmed
  8. Casson PR, et al. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod, 2000;15:2129-2132.
  9. Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA: Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10. Pubmed
  10. Barrett-Connor E, Khaw KT, Yen SS: A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986 Dec 11;315(24):1519-24. Pubmed
  11. Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM, Wang TJ, Knapp PE, D’Agostino RB Sr, Bhasin S, Vasan RS: Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006 Aug 1;145(3):176-84. Pubmed
  12. Crosbie D, Black C, McIntyre L, Royle PL, Thomas S: Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114. Pubmed
  13. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7.
  14. Mattison JA, Lane MA, Roth GS, Ingram DK: Calorie restriction in rhesus monkeys. Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46. Pubmed
  15. Roberts E: The importance of being dehydroepiandrosterone sulfate (in the blood of primates): a longer and healthier life? Biochem Pharmacol. 1999 Feb 15;57(4):329-46. Pubmed
  16. Leblanc M, Labrie C, Belanger A, Candas B, Labrie F: Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey. J Clin Endocrinol Metab. 2003 Sep;88(9):4293-302. Pubmed
External Links
Resource Link
KEGG Compound C01227 Link_out
PubChem Compound 5881 Link_out
PubChem Substance 46508824 Link_out
ChemSpider 5670 Link_out
ChEBI 28689 Link_out
ChEMBL 28689 Link_out
Therapeutic Targets Database DNC001146 Link_out
PharmGKB PA451993 Link_out
IUPHAR 2370 Link_out
Guide to Pharmacology 2370 Link_out
HET AND Link_out
Wikipedia http://en.wikipedia.org/wiki/Dehydroepiandrosterone Link_out
ATC Codes
  • A14AA07
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (19.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Steroid Delta-isomerase

Pharmacological action: unknown

A 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)- steroid

Organism class: bacterial
UniProt ID: P07445 Link_out
Gene: ksi
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Bile salt sulfotransferase

Pharmacological action: unknown

Catalyzes the sulfation of steroids and bile acids in the liver and adrenal glands

Organism class: human
UniProt ID: Q06520 Link_out
Gene: SULT2A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

3. Cholesterol oxidase

Pharmacological action: unknown

Cholesterol + O(2) = cholest-4-en-3-one + H(2)O(2)

Organism class: bacterial
UniProt ID: P22637 Link_out
Gene: choB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

4. Estradiol 17-beta-dehydrogenase 1

Pharmacological action: unknown

Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH

Organism class: human
UniProt ID: P14061 Link_out
Gene: HSD17B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. Sulfotransferase family cytosolic 2B member 1

Pharmacological action: unknown

Catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Sulfates hydroxysteroids like DHEA. Isoform 1 preferentially sulfonates cholesterol, and isoform 2 avidly sulfonates pregnenolone but not cholesterol

Organism class: human
UniProt ID: O00204 Link_out
Gene: SULT2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A7

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20