Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ
4-dione), also known as androst-4-ene-3,17-dione, is an
endogenous weak
androgen steroid hormone and
intermediate in the
biosynthesis of
estrone and of
testosterone from
dehydroepiandrosterone (DHEA). It is closely related to
androstenediol
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 dehydroep ...
(androst-5-ene-3β,17β-diol).
Biological function
Androstenedione is a precursor of testosterone and other androgens, as well as of estrogens like estrone, in the body. In addition to functioning as an endogenous
prohormone, androstenedione also has weak androgenic activity in its own right.
Androstenedione has been found to possess some
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 ...
ic activity, similarly to other DHEA metabolites.
However, in contrast to
androstenediol
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 dehydroep ...
, its
affinity for the
estrogen receptors is very low, with less than 0.01% of the affinity of
estradiol for both the
ERα and
ERβ.
Adrenarche
In children aged 6 to 8 years old, there is a rise in androstenedione secretion along with DHEA during
adrenarche. This rise in androstenedione and DHEA is hypothesized to play a crucial role for learning social, cultural and ecological skills, such as the development and understanding of sexual attraction. Furthermore, it is thought that androstenedione plays a role in levels of aggression and competition in boys, as a positive correlation between the two were observed, while testosterone levels were below detection.
Biochemistry
Biosynthesis
Androstenedione is the common
precursor
Precursor or Precursors may refer to:
* Precursor (religion), a forerunner, predecessor
** The Precursor, John the Baptist
Science and technology
* Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
of the androgen and estrogen
sex hormones.
Androstenedione can be biosynthesized in one of two ways. The primary pathway involves conversion of
17α-hydroxypregnenolone to DHEA by way of
17,20-lyase, with subsequent conversion of DHEA to androstenedione via the enzyme
3β-hydroxysteroid dehydrogenase. The secondary pathway involves conversion of
17α-hydroxyprogesterone, most often a precursor to
cortisol, to androstenedione directly by way of
17,20-lyase. Thus, 17,20-lyase is required for the synthesis of androstenedione, whether immediately or one step removed.
Androstenedione is produced in the
adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex ...
s and the
gonads. The production of adrenal androstenedione is governed by
adrenocorticotrophic hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...
(ACTH), whereas production of gonadal androstenedione is under control by the
gonadotropins. In
premenopausal women, the adrenal glands and
ovaries
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
each produce about half of the total androstenedione (about 3 mg/day). After
menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
, androstenedione production is about halved, due primarily to the reduction of the steroid secreted by the ovary. Nevertheless, androstenedione is the principal steroid produced by the
postmenopausal ovary.
Some androstenedione is also secreted into the
plasma, and may be converted in peripheral tissues to testosterone and estrogens.
Metabolism
Androstenedione is converted to either
testosterone or
estrone. Conversion of androstenedione to testosterone requires the enzyme
17β-hydroxysteroid dehydrogenase. Androstenedione is released into the blood by
theca cells
In biology, a theca (plural thecae) is a sheath or a covering.
Botany
In botany, the theca is related to plant's flower anatomy. The theca of an angiosperm consists of a pair of microsporangia that are adjacent to each other and share a comm ...
. Conversion of androstenedione to estrone requires the enzyme
aromatase. Androstenedione is a substrate for
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 ...
production in
granulosa cells
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete (called an oocyte or egg) in the ovary of mammals.
Structure and function
In the primordial ovarian follicle, and ...
which produce aromatase. Thus, theca cells and granulosa cells work together to form estrogens.
Androstanedione is a
5α-reduced metabolite of 4-androstenedione which serves as an intermediate in the biosynthesis of the androgen and
neurosteroid androsterone
Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an endogenous steroid hormone, neurosteroid, and putative pheromone. It is a weak androgen with a potency that is approximately 1/7 that of testosterone. Androsterone is a metabolite of tes ...
.
Levels
Levels are normally 30–200 ng/dL (1.0–7.0 nmol/L) in females and 40–150 ng/dL (1.4–5.2 nmol/L) in males.
Pharmacology
Androstenedione has been shown to increase serum testosterone levels over an eight-hour period in men when taken as a single oral dose of 300 mg per day, but a dose of 100 mg had no significant effect on serum testosterone.
However, serum levels of estradiol increased following both the 100 mg and 300 mg doses.
The study also reported that the serum level of estrogens and testosterone produced varied widely between individuals.
A 2006 review paper summarized several studies that examined the effect of androstenedione on
strength training.
At dosages of 50 mg or 100 mg per day, androstenedione had no effect on muscle strength or size, or on body fat levels.
One study used a daily dosage of 300 mg of androstenedione combined with several other supplements, and also found no increase in strength when compared to a control group that did not take the supplements.
The review authors speculate that sufficiently high doses may indeed lead to increased muscle size and strength.
However, due to the federal ban on androstenedione supplements, it is difficult to carry out new research on its effects.
The review authors conclude that individuals should not use androstenedione supplements due to the lack of evidence of beneficial effects, the wide variation in individual responses to the supplement, and the risk of unknown side effects.
Medical use
Under the brand name Metharmon-F and in combination with
sex steroids (
pregnenolone
Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocor ...
,
testosterone,
estrone,
androstenediol
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 dehydroep ...
) and
thyroid hormone (
desiccated thyroid), androstenedione is or has been marketed for medical use in
Thailand
Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
.
Chemistry
Androstenedione, also known as androst-4-ene-3,17-dione, is a
naturally occurring androstane steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
and a
17-ketosteroid. It is closely related structurally to
androstenediol
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 dehydroep ...
(A5; androst-5-ene-3β,17β-diol),
dehydroepiandrosterone (DHEA; androst-5-en-3β-ol-17-one), and
testosterone (androst-4-en-17β-ol-3-one), as well as to
5α-androstanedione
Androstanedione, also known as 5α-androstanedione or as 5α-androstane-3,17-dione, is a naturally occurring androstane (5α-androstane) steroid and an endogenous metabolite of androgens like testosterone, dihydrotestosterone (DHT), dehydroepia ...
(5α-androstane-3,17-dione) and
estrone (estra-1,3,5(10)-triene-3-ol-17-one or 19-norandrost-1,3,5(10)-triene-3-ol-17-one).
History
Use as a supplement
Androstenedione was manufactured as a
dietary supplement, often called ''andro'' or ''andros'' for short. ''
Sports Illustrated
''Sports Illustrated'' (''SI'') is an American sports magazine first published in August 1954. Founded by Stuart Scheftel, it was the first magazine with circulation over one million to win the National Magazine Award for General Excellence tw ...
'' credits
Patrick Arnold
Patrick Arnold (born 1966) is an American organic chemist known for introducing androstenedione, 1-androstenediol, and methylhexanamine into the dietary supplement market, and for creating the designer steroid tetrahydrogestrinone, also known as ...
with introducing androstenedione to the North American market.
Androstenedione was legal and able to be purchased
over the counter, and, as a consequence, it was in common use in
Major League Baseball
Major League Baseball (MLB) is a professional baseball organization and the oldest major professional sports league in the world. MLB is composed of 30 total teams, divided equally between the National League (NL) and the American League (A ...
throughout the 1990s by record-breaking sluggers like
Mark McGwire.
Barry R. McCaffrey
Barry Richard McCaffrey (born November 17, 1942) is a retired United States Army general and current news commentator, professor and business consultant who served in President Bill Clinton's Cabinet as the Director of the Office of National Drug ...
, in his capacity as director of the
White House
The White House is the official residence and workplace of the president of the United States. It is located at 1600 Pennsylvania Avenue NW in Washington, D.C., and has been the residence of every U.S. president since John Adams in ...
Office of National Drug Control Policy from 1996 to 2001, determined that androstenedione could not be classified as an anabolic steroid because there is no proof that it promotes muscle growth.
Society and culture
Regulation
Androstenedione is banned by the
World Anti-Doping Agency, and from the
Olympic Games
The modern Olympic Games or Olympics (french: link=no, Jeux olympiques) are the leading international sporting events featuring summer and winter sports competitions in which thousands of athletes from around the world participate in a multi ...
. The International Olympic Committee in 1997 banned androstenedione and placed it under the category of androgenic-anabolic steroids.
Androstenedione is banned by MLB, the NFL, USOC, NCAA, and by the NBA.
On March 12, 2004, the Anabolic Steroid Control Act of 2004 was introduced into the United States Senate. It amended the
Controlled Substance Act to place both
anabolic steroids and
prohormones on a list of
controlled substances, making possession of the banned substances a federal crime. The law took effect on January 20, 2005. However, androstenedione was legally defined as an anabolic steroid, even though there is scant evidence that androstenedione itself is anabolic in nature. On April 11, 2004, the United States
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
banned the sale of androstenedione, citing that the drug poses significant health risks commonly associated with steroids. Androstenedione is currently banned by the
U.S. military.
References
Androstenedione
; Citations
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Androstanes
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