Androstenediol

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Androstenediol
5-Androstenediol.png
Androstenediol molecule ball.png
Clinical data
Synonyms A5; Δ5-Diol; Androstenediol; Androst-5-ene-3β,17β-diol; Hermaphrodiol; HE2100
Routes of
administration
By mouth
Drug class Androgen; Anabolic steroid
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
ECHA InfoCard 100.007.553 Edit this at Wikidata
Chemical and physical data
Formula C19H30O2
Molar mass 290.44 g/mol
3D model (JSmol)
  (verify)

Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ5-diol), also known as androst-5-ene-3β,17β-diol, is an endogenous weak androgen and estrogen steroid hormone and intermediate in the biosynthesis of testosterone from dehydroepiandrosterone (DHEA). It is closely related to androstenedione (androst-4-ene-3,17-dione).

Biological activity[edit]

Androstenediol is a direct metabolite of the most abundant steroid produced by the human adrenal cortex, DHEA. It is less androgenic than the related compound, Δ4-androstenediol, and has been found to stimulate the immune system. When administered to rats, androstenediol, in vivo, has approximately 1.4% of the androgenicity of DHEA, 0.54% of the androgenicity of androstenedione, and 0.21% of the androgenicity of testosterone.[1]

Androstenediol possesses potent estrogenic activity, similarly to DHEA and 3β-androstanediol.[2] It has approximately 6% and 17% of the affinity of estradiol at the ERα and ERβ, respectively.[3] Although androstenediol has far lower affinity for the ERs compared to the major estrogen estradiol, it circulates at approximately 100-fold higher concentrations, and so is thought may play a significant role as an estrogen in the body.[4]

Chemistry[edit]

Androstenediol, also known as androst-5-ene-3β,17β-diol, is a naturally occurring androstane steroid.[5] It is closely related structurally to androstenedione (A4; androst-4-ene-3,17-dione), dehydroepiandrosterone (DHEA; androst-5-en-3β-ol-17-one), and testosterone (androst-4-en-17β-ol-3-one), as well as to 3β-androstanediol (5α-androstane-3β,17β-diol).[5]

Research[edit]

Radiation countermeasure[edit]

Androstenediol has been investigated for use as a radiation countermeasure. Its value as a radiation countermeasure is based mainly on its stimulation of production of white blood cells and platelets.[6] Its potential use as a radiation countermeasure was developed by the Armed Forces Radiobiology Research Institute (AFRRI) and subsequently studied by AFRRI and Hollis-Eden Pharmaceuticals under the proposed brand name Neumune for the treatment of acute radiation syndrome.[6][7]

The clinical trials with rhesus monkeys were successful. According to the Hollis-Eden report, only 12.5% of the 40 Neumune-treated animals died versus 32.5% in the placebo group.[8]

Hollis-Eden had applied for a contract from the U.S. Government under the BioShield Request for Proposals (RFP) for radiation countermeasures. After being encouraged for 2.5 years that Neumune was in the competitive range, on March 9, 2007, the RFP was canceled by HHS. According to HHS, "the product was no longer in the competitive range".[9][10] No further explanation was given. As a result, Hollis-Eden has now withdrawn from the radiation countermeasure field.

Additional images[edit]

Steroidogenesis, with androstenediol at bottom left.

References[edit]

  1. ^ Coffey, DS (1988) "Androgen action and the sex accessory tissues". In E Knobil, J Neill (eds), The Physiology of Reproduction. Raven Press, New York, pp 1081-1119.
  2. ^ Hackenberg, Reinhard; Turgetto, Inga; Filmer, Angelika; Schulz, Klaus-Dieter (1993). "Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androst-5-ene-3β,17β-diol in human mammary cancer cells". The Journal of Steroid Biochemistry and Molecular Biology. 46 (5): 597–603. doi:10.1016/0960-0760(93)90187-2. ISSN 0960-0760. 
  3. ^ Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (1997). "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology. 138 (3): 863–70. doi:10.1210/endo.138.3.4979. PMID 9048584. 
  4. ^ Rob Bradbury (30 January 2007). Cancer. Springer Science & Business Media. pp. 43–. ISBN 978-3-540-33120-9. 
  5. ^ a b J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 86–. ISBN 978-1-4757-2085-3. 
  6. ^ a b Whitnall MH, Elliott TB, Harding RA, Inal CE, Landauer MR, Wilhelmsen CL, McKinney L, Miner VL, Jackson WE 3rd, Loria RM, Ledney GD, Seed TM (2000). "Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice". Int. J. Immunopharmacol. 22 (1): 1–14. doi:10.1016/s0192-0561(99)00059-4. PMID 10684984. 
  7. ^ Grace MB, Singh VK, Rhee JG, Jackson WE 3rd, Kao TC, Whitnall MH (2012). "5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis". J. Radiat. Res. 53 (6): 840–853. doi:10.1093/jrr/rrs060. PMC 3483857Freely accessible. PMID 22843381. 
  8. ^ Hollis-Eden Pharmaceuticals Reports Publication of Results Demonstrating the Ability of NEUMUNE(R) to Increase Survival in a Primate Model of Lethal Radiation Injury, February 26, 2007.
  9. ^ Government Nukes Hollis-Eden's Radiation Drug, by Val Brickates Kennedy and Angela Moore, March 8, 2007
  10. ^ US cancels radiation contract with Hollis-Eden Archived 2007-09-12 at Archive.is, March 9, 2007