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.

Androstenediol possesses potent estrogenic activity, similarly to DHEA and 3β-androstanediol. It has approximately 6% and 17% of the affinity of estradiol at the ERα and ERβ, respectively. 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.

Chemistry

Androstenediol, also known as androst-5-ene-3β,17β-diol, is a naturally occurring androstane steroid. 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).

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.

Synthesis The chemical synthesis entails the reduction of the 17-keto group of DHEA:Butenandt, Adolf; Hanisch, Günter (1935). "Über die Umwandlung des Dehydro-androsterons in Δ4-Androsten-ol-(17)-0n-(3) (Testosteron); ein Weg zur Darstellung des Testosterons aus Cholesterin (Vorläuf. Mitteil.)". Berichte der deutschen chemischen Gesellschaft (A and B Series). 68 (9): 1859–1862. doi:10.1002/cber.19350680937.Ruzicka, L.; Wettstein, A. (1935). "Sexualhormone VII. Über die künstliche Herstellung des Testikelhormons Testosteron (Androsten-3-on-17-ol)". Helvetica Chimica Acta. 18 (1): 1264–1275. doi:10.1002/hlca.193501801176.Zeynizadeh, Behzad Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2003, vol. 58, # 12. p. 1220 – 1226.

Esters A number of esters of Androstenediol have been prepared: 3-Ac: [1639-43-6] 17-Ac: [5937-72-4] Di-Ac: [2099-26-5] Androstenediol dipropionate [2297-30-5]. Bisexovis, Bisexovister, Ginandrin, Stenandiol.

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. 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.

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.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.

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".Government Nukes Hollis-Eden's Radiation Drug, by Val Brickates Kennedy and Angela Moore, March 8, 2007US cancels radiation contract with Hollis-Eden , March 9, 2007 No further explanation was given. As a result, Hollis-Eden has now withdrawn from the radiation countermeasure field.

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