Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ⁵-diol), also known as androst-5-ene-3β,17β-diol, is an endogenous weak

androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...

and

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...

and intermediate in the biosynthesis of

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

from

dehydroepiandrosterone Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It fun ...

(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

ic 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

icity of DHEA, 0.54% of the androgenicity of androstenedione, and 0.21% of the androgenicity of testosterone. Androstenediol possesses potent

ic activity, similarly to DHEA and

3β-androstanediol 3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT) ...

. 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 Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

, 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 A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...

steroid. It is closely related structurally to androstenedione (A4; androst-4-ene-3,17-dione),

(DHEA; androst-5-en-3β-ol-17-one), and

(androst-4-en-17β-ol-3-one), as well as to

(5α-androstane-3β,17β-diol).

Derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

s 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

s 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

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

s. 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 trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s 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 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".US 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.

Additional images

References

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