Dehydroepiandrosterone

Source: Wikipedia, the free encyclopedia.
(Redirected from
DHEA
)
This article is about DHEA as a hormone. For its use as a medication or supplement, see
DHEA (disambiguation). For the precursor hormone of DHEA produced mainly in the adrenal cortex, DHEA sulfate or DHEA-S, see Dehydroepiandrosterone sulfate
.
Dehydroepiandrosterone
Names
IUPAC name
3β-Hydroxyandrost-5-en-17-one
Systematic IUPAC name
(3aS,3bR,7S,9aR,9bS,11aS)-7-Hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-1-one
Other names
Androstenolone; Prasterone; Androst-5-en-3β-ol-17-one; 5,6-Didehydroepiandrosterone;[1] Dehydroisoepiandrosterone
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.000.160 Edit this at Wikidata
UNII
  • 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 checkY
    Key: FMGSKLZLMKYGDP-USOAJAOKSA-N checkY
  • O=C3[C@]2(CC[C@@H]1[C@@]4(C(=C/C[C@H]1[C@@H]2CC3)\C[C@@H](O)CC4)C)C
Properties
C19H28O2
Molar mass 288.424 g/mol
Melting point 148.5
Pharmacology
QA14AA07 (WHO)
G03EA03 (WHO) (combination with estrogen)
prasterone sodium sulfate
)
Pharmacokinetics:
50%[2]
Hepatic[2]
DHEA: 25 minutes[3]
DHEA-S: 11 hours[3]
Urine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Dehydroepiandrosterone (DHEA), also known as androstenolone, is an

sex steroids both in the gonads and in various other tissues.[4][8][9] However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors,[10] and acting as a neurosteroid and modulator of neurotrophic factor receptors.[11]

In the United States, DHEA is sold as an

over-the-counter supplement, and medication called prasterone
.

Biological function

As an androgen

DHEA and other adrenal androgens such as

axillary hair growth, adult-type body odor, increased oiliness of hair and skin, and mild acne.[12][13][14] DHEA is potentiated locally via conversion into testosterone and dihydrotestosterone (DHT) in the skin and hair follicles.[4] Women with complete androgen insensitivity syndrome (CAIS), who have a non-functional androgen receptor (AR) and are immune to the androgenic effects of DHEA and other androgens, have absent or only sparse/scanty pubic and axillary hair and body hair in general, demonstrating the role of DHEA and other androgens in body hair development at both adrenarche and pubarche.[15][16][17][18]

As an estrogen

DHEA is a weak estrogen.[4][10][19] In addition, it is transformed into potent estrogens such as estradiol in certain tissues such as the vagina, and thereby produces estrogenic effects in such tissues.[4]

As a neurosteroid

As a neurosteroid and neurotrophin, DHEA has important effects in the central nervous system.[20][21][22]

Biological activity

Hormonal activity

Androgen receptor

Although it functions as an endogenous

full agonists like testosterone, it can actually behave more like an antagonist depending on circulating testosterone and dihydrotestosterone (DHT) levels, and hence, like an antiandrogen. However, its affinity for the receptor is very low, and for that reason, is unlikely to be of much significance under normal circumstances.[19][23]

Estrogen receptors

In addition to its affinity for the androgen receptor, DHEA has also been found to bind to (and activate) the ERα and ERβ estrogen receptors with Ki values of 1.1 μM and 0.5 μM, respectively, and EC50 values of >1 μM and 200 nM, respectively. Though it was found to be a partial agonist of the ERα with a maximal efficacy of 30–70%, the concentrations required for this degree of activation make it unlikely that the activity of DHEA at this receptor is physiologically meaningful. Remarkably however, DHEA acts as a full agonist of the ERβ with a maximal response similar to or actually slightly greater than that of estradiol, and its levels in circulation and local tissues in the human body are high enough to activate the receptor to the same degree as that seen with circulating estradiol levels at somewhat higher than their maximal, non-ovulatory concentrations; indeed, when combined with estradiol with both at levels equivalent to those of their physiological concentrations, overall activation of the ERβ was doubled.[10][19]

Other nuclear receptors

DHEA does not bind to or activate the

IGFBP1.[19][27]

Neurosteroid activity

Neurotransmitter receptors

DHEA has been found to directly act on several

negative allosteric modulator of the GABAA receptor, and as an agonist of the σ1 receptor.[28][25]

Neurotrophin receptors

Main article: Neurotrophic factor receptor

In 2011, the surprising discovery was made that DHEA, as well as its sulfate ester,

neurotrophin receptors may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases.[25][29]

Microtubule-associated protein 2

Similarly to

3β-methoxypregnenolone (MAP-4343), and progesterone, DHEA has been found to bind to microtubule-associated protein 2 (MAP2), specifically the MAP2C subtype (Kd = 27 μM).[25] However, it is unclear whether DHEA increases binding of MAP2 to tubulin like pregnenolone.[25]

ADHD

Some research has shown that DHEA levels are too low in people with ADHD, and treatment with methylphenidate or bupropion (stimulant type of medications) normalizes DHEA levels. [32]

Other activity

G6PDH inhibitor

DHEA is an

immunomodulating activities of DHEA (with some experimental evidence to support this notion available).[33][34][35][36] However, it has also been said that inhibition of G6PDH activity by DHEA in vivo has not been observed and that the concentrations required for DHEA to inhibit G6PDH in vitro are very high, thus making the possible contribution of G6PDH inhibition to the effects of DHEA uncertain.[34]

Cancer

DHEA supplements have been promoted in supplement form for its claimed cancer prevention properties; there is no scientific evidence to support these claims.[37]

Miscellaneous

DHEA has been found to competitively inhibit TRPV1.[28]

Biochemistry

steroidogenesis, showing DHEA at left among the androgens.[38]

Biosynthesis

DHEA is produced in the

17α-hydroxypregnenolone as intermediates.[42] It is derived mostly from the adrenal cortex, with only about 10% being secreted from the gonads.[43][44][45] Approximately 50 to 70% of circulating DHEA originates from desulfation of DHEA-S in peripheral tissues.[43] DHEA-S itself originates almost exclusively from the adrenal cortex, with 95 to 100% being secreted from the adrenal cortex in women.[39][45]

Increasing endogenous production

Regular exercise is known to increase DHEA production in the body.[46][47] Calorie restriction has also been shown to increase DHEA in primates.[48] 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.[49]

Distribution

In the circulation, DHEA is mainly bound to albumin, with a small amount bound to sex hormone-binding globulin (SHBG).[50][51] The small remainder of DHEA not associated with albumin or SHBG is unbound and free in the circulation.[50]

DHEA easily crosses the blood–brain barrier into the central nervous system.[41]

Metabolism

DHEA is transformed into DHEA-S by

exogenous DHEA is administered orally.[52] Levels of DHEA-S in circulation are approximately 250 to 300 times those of DHEA.[20] DHEA-S in turn can be converted back into DHEA in peripheral tissues via steroid sulfatase (STS).[54][55]

The

duration of DHEA.[57][20]

7β-hydroxyepiandrosterone, as well as androstenediol and androstenedione.[8]

Pregnancy

During

15α-hydroxy-DHEA in the fetal liver as intermediates in the production of the estrogens estriol and estetrol, respectively.[58]

Levels

Prior to puberty in humans, DHEA and DHEA-S levels elevate upon differentiation of the zona reticularis of the adrenal cortex.[25] Peak levels of DHEA and DHEA-S are observed around age 20, which is followed by an age-dependent decline throughout life eventually back to prepubertal concentrations.[25] Plasma levels of DHEA in adult men are 10 to 25 nM, in premenopausal women are 5 to 30 nM, and in postmenopausal women are 2 to 20 nM.[25] Conversely, DHEA-S levels are an order of magnitude higher at 1–10 μM.[25] Levels of DHEA and DHEA-S decline to the lower nanomolar and micromolar ranges in men and women aged 60 to 80 years.[25]

DHEA levels are as follows:[59]

  • Adult men: 180–1250 ng/dL
  • Adult women: 130–980 ng/dL
  • Pregnant women: 135–810 ng/dL
  • Prepubertal children (<1 year): 26–585 ng/dL
  • Prepubertal children (1–5 years): 9–68 ng/dL
  • Prepubertal children (6–12 years): 11–186 ng/dL
  • Adolescent boys (Tanner II–III): 25–300 ng/dL
  • Adolescent girls (Tanner II–III): 69–605 ng/dL
  • Adolescent boys (Tanner IV–V): 100–400 ng/dL
  • Adolescent girls (Tanner IV–V): 165–690 ng/dL

Measurement

As almost all DHEA is derived from the adrenal glands, blood measurements of DHEA-S/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 DHEA-S.[60]

Chemistry

See also:
List of androgens/anabolic steroids and List of neurosteroids

DHEA, also known as androst-5-en-3β-ol-17-one, is a

17-ketosteroid.[61] It is closely related structurally to androstenediol (androst-5-ene-3β,17β-diol), androstenedione (androst-4-ene-3,17-dione), and testosterone (androst-4-en-17β-ol-3-one).[61] DHEA is the 5-dehydro analogue of epiandrosterone (5α-androstan-3β-ol-17-one) and is also known as 5-dehydroepiandrosterone or as δ5-epiandrosterone.[61]

Isomers

The term "dehydroepiandrosterone" is ambiguous chemically because it does not include the specific positions within epiandrosterone at which hydrogen atoms are missing. DHEA itself is 5,6-didehydroepiandrosterone or 5-dehydroepiandrosterone. A number of naturally occurring isomers also exist and may have similar activities. Some isomers of DHEA are

4-dehydroepiandrosterone.[62] These isomers are also technically "DHEA", since they are dehydroepiandrosterones in which hydrogens are removed from the epiandrosterone
skeleton.

Dehydroandrosterone (DHA) is the 3α-epimer of DHEA and is also an endogenous androgen.

History

See also: Prasterone § History

DHEA was first isolated from human urine in 1934 by Adolf Butenandt and Kurt Tscherning.[63]

See also

References

  1. ISBN 978-1-4200-7636-3
    .
  2. ^
    ISBN 978-1-59259-303-3
    .
  3. ^
    ISBN 978-1-85070-763-9
    .
  4. ^
    PMID 16293766
    .
  5. ^ William F Ganong MD, 'Review of Medical Physiology', 22nd Ed, McGraw Hill, 2005, p. 362.
  6. ^ The Merck Index, 13th Edition, 7798
  7. ISBN 978-1-57954-942-8
    . DHEA (Dehydroepiandrosterone) is a common hormone produced in the adrenal glands, the gonads, and the brain.
  8. ^
    S2CID 30489004
    .
  9. ISBN 978-3-11-010661-9
    . Retrieved 25 May 2012.
  10. ^
    PMID 16684650
    .
  11. S2CID 30733847
    .
  12. ISBN 978-0-7817-4059-3
    .
  13. ISBN 978-1-4200-4272-6
    .
  14. ISBN 978-93-5025-369-4
    .
  15. ISBN 978-1-4612-5064-7
    .
  16. ISBN 978-0-323-39206-8
    .
  17. ISBN 978-81-312-3481-5
    .
  18. ISBN 978-0-07-135455-4
    .
  19. ^
    PMID 15994348
    .
  20. ^
    ISBN 978-1-4020-6854-6
    .
  21. ISBN 978-3-527-63397-5
    .
  22. ISBN 978-0-444-53631-0
    .
  23. PMID 16159155
    .
  24. PMID 21747041
    .
  25. ^
    PMID 26908835
    .
  26. ISBN 978-1-4398-3884-6
    .
  27. S2CID 26893297
    .
  28. ^
    ISBN 978-1-4614-5559-2
    .
  29. ^
    PMID 21541365
    .
  30. ^
    PMID 25330101
    .
  31. S2CID 26914550
    .
  32. S2CID 11041447
    .
  33. ^
    S2CID 11871872
    .
  34. ^
    PMID 12097275
    .
  35. PMID 16952912
    .
  36. S2CID 32258529
    .
  37. ISBN 9780944235713
    .
  38. ISSN 2002-4436
    .
  39. ^
    ISBN 978-0-444-51830-9
    .
  40. ISBN 978-3-319-15060-4
    .
  41. ^
    ISBN 978-1-4377-2333-5
    .
  42. ^
    PMID 17945481
    .
  43. ^
    ISBN 978-1-934115-19-0
    .
  44. ISBN 978-3-540-33713-3
    .
  45. ^
    ISBN 978-3-540-26861-1
    .
  46. S2CID 20583279
    .
  47. PMID 11909881
    .
  48. S2CID 41481691
    ..
  49. PMID 9933021
    ..
  50. ^
    ISBN 978-0-8247-5504-1
    .
  51. ISBN 978-0-7817-1750-2
    .
  52. ^
    PMID 26213785
    .
  53. ISBN 978-1-59259-832-8
    .
  54. ISBN 978-0-203-30121-0
    .
  55. ISBN 978-1-59454-426-2
    .
  56. ^
    ISBN 978-0-323-08704-9
    .
  57. ISBN 978-3-11-016111-3
    .
  58. PMID 2942557
    .
  59. ^ "DHEA (Dehydroepiandrosterone)" (PDF). Quest Diagnostics. Archived from the original (PDF) on Sep 27, 2020.
  60. PMID 14737959
    .
  61. ^
    ISBN 978-1-4757-2085-3
    .
  62. ISBN 978-3-662-25863-7
    .
  63. PMID 11478328
    .

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=Dehydroepiandrosterone&oldid=1217526493"
This page is based on the copyrighted Wikipedia article: DHEA. Articles is available under the CC BY-SA 3.0 license; additional terms may apply.Privacy Policy