Chemistry:Androstenediol
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| Other names | A5; Δ5-Diol; Androstenediol; Androst-5-ene-3β,17β-diol; Hermaphrodiol; HE2100 |
| Routes of administration | By mouth |
| Drug class | Androgen; Anabolic steroid |
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| Formula | C19H30O2 |
| Molar mass | 290.447 g·mol−1 |
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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
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
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]
Derivatives and analogues of androstenediol, such as the 17α-substituted methandriol (17α-methylandrostenediol) and ethinylandrostenediol (17α-ethynylandrostenediol) as well as the naturally occurring 19-norandrostane derivative norandostenediol (19-nor-5-androstenediol), have been synthesized and studied. Methandriol and its esters are androgens and anabolic steroids while ethinylandrostenediol is an estrogen.
Research
Radiation countermeasure
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
References
- ↑ "Androgen action and the sex accessory tissues". The Physiology of Reproduction.. New York: Raven Press. 1988. pp. 1081–1119.
- ↑ "Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androst-5-ene-3 beta,17 beta-diol in human mammary cancer cells". The Journal of Steroid Biochemistry and Molecular Biology 46 (5): 597–603. November 1993. doi:10.1016/0960-0760(93)90187-2. PMID 8240982.
- ↑ "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology 138 (3): 863–870. March 1997. doi:10.1210/endo.138.3.4979. PMID 9048584.
- ↑ Cancer. Springer Science & Business Media. 30 January 2007. pp. 43–. ISBN 978-3-540-33120-9. https://books.google.com/books?id=fdtDAAAAQBAJ&pg=PA43.
- ↑ 5.0 5.1 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 86–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA86.
- ↑ 6.0 6.1 "Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice". Int. J. Immunopharmacol. 22 (1): 1–14. 2000. doi:10.1016/s0192-0561(99)00059-4. PMID 10684984.
- ↑ "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. 2012. doi:10.1093/jrr/rrs060. PMID 22843381.
- ↑ 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.
- ↑ Government Nukes Hollis-Eden's Radiation Drug, by Val Brickates Kennedy and Angela Moore, March 8, 2007
- ↑ US cancels radiation contract with Hollis-Eden , March 9, 2007
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