Androstenedione
Encyclopedia
Androstenedione is a 19-carbon
steroid hormone
produced in the adrenal gland
s and the gonad
s as an intermediate step in the biochemical
pathway that produces the androgen
testosterone
and the estrogen
s estrone
and estradiol
.
Androstenedione is the common precursor
of male and female sex hormones. Some androstenedione is also secreted into the plasma
, and may be converted in peripheral tissues to testosterone and estrogens.
Androstenedione can be synthesized in one of two ways. The primary pathway involves conversion of 17-hydroxypregnenolone
to dehydroepiandrosterone
by way of 17,20-lyase, with subsequent conversion of dehydroepiandrosterone
to androstenedione via the enzyme 3-β-hydroxysteroid dehydrogenase. The secondary pathway involves conversion of 17-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 further converted to either testosterone
or estrogen
. Conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase, while conversion of androstenedione to estrogen (e.g. estrone
and estradiol
) requires the enzyme aromatase
.
The production of adrenal androstenedione is governed by ACTH, whereas production of gonadal androstenedione is under control by gonadotropin
s. In premenopausal women, the adrenal glands and ovaries each produce about half of the total androstendione (about 3 mg/day). After menopause
,
androstenedione production is about halved, primarily due to the reduction of the steroid secreted by the ovary. Nevertheless, androstenedione is the principal steroid produced by the postmenopausal ovary.
production in granulosa cells, since these cells lack 17,20 lyase required for androstenedione. Similarly, theca cells lack the enzyme aromatase required to make estrogens themselves. Thus, theca cells and granulosa cells work together to form estrogen.
, often called andro (or andros) for short. Sports Illustrated
credits Patrick Arnold
for introducing androstenedione to the North American market. Andro was legal and able to be purchased over the counter and consequently it was in common use in Major League Baseball
throughout the 1990s by record-breaking sluggers like Mark McGwire
. The supplement is banned by the World Anti-Doping Agency
, and hence from the Olympic Games
.
The International Olympic Committee in 1997 banned androstenedione and placed it under the category of androgenic-anabolic steroids.
Androstenedione is banned by the USOC and NCA but not by MLB and the NBA.
Barry R. McCaffrey, the director of the White House's Office of National Drug Control Policy, attempted to determine whether androstenedione could be classified as an anabolic steroid in July of 1999. However, it could not because there is no proof of it promoting muscle growth.
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 steroid
s and prohormone
s on a list of controlled substance
s, making possession of the banned substances a federal crime. The law took effect on January 20, 2005. Surprisingly, 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
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
.
. At dosages of 50 mg or 100 mg per day, andro 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 positive and negative 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.
Because androstenedione is converted in part to estrogens, people taking this supplement may have estrogenic side effects, although none of the studies cited above used a sufficiently high dosage to draw any conclusions.
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
produced in the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s and the gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s as an intermediate step in the biochemical
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
pathway that produces the androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
and the estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
s estrone
Estrone
Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
and estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
.
Synthesis
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...
of male and female sex hormones. Some androstenedione is also secreted into the plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, and may be converted in peripheral tissues to testosterone and estrogens.
Androstenedione can be synthesized in one of two ways. The primary pathway involves conversion of 17-hydroxypregnenolone
17-Hydroxypregnenolone
17-Hydroxypregnenolone , is a C21 steroid that is obtained by hydroxylation of pregnenolone at the C17α position. This step is performed by the mitochondrial cytochrome P450 enzyme 17α-hydroxylase that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty...
to dehydroepiandrosterone
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
by way of 17,20-lyase, with subsequent conversion of dehydroepiandrosterone
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
to androstenedione via the enzyme 3-β-hydroxysteroid dehydrogenase. The secondary pathway involves conversion of 17-hydroxyprogesterone
17-Hydroxyprogesterone
17-Hydroxyprogesterone is a C-21 steroid hormone produced during the synthesis of glucocorticoids and sex steroids.As a hormone, 17OHP also interacts with the progesterone receptor.-Production:...
, most often a precursor to cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
, 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 further converted to either testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
or estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
. Conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase, while conversion of androstenedione to estrogen (e.g. estrone
Estrone
Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
and estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
) requires the enzyme aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
.
The production of adrenal androstenedione is governed by ACTH, whereas production of gonadal androstenedione is under control by gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s. In premenopausal women, the adrenal glands and ovaries each produce about half of the total androstendione (about 3 mg/day). After menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
,
androstenedione production is about halved, primarily due to the reduction of the steroid secreted by the ovary. Nevertheless, androstenedione is the principal steroid produced by the postmenopausal ovary.
Endocrine function
In females, androstenedione is released into the blood by theca cells. The function of this is to provide androstenedione substrate for estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
production in granulosa cells, since these cells lack 17,20 lyase required for androstenedione. Similarly, theca cells lack the enzyme aromatase required to make estrogens themselves. Thus, theca cells and granulosa cells work together to form estrogen.
History
Androstenedione was manufactured as a dietary supplementDietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
, often called andro (or andros) for short. Sports Illustrated
Sports Illustrated
Sports Illustrated is an American sports media company owned by media conglomerate Time Warner. Its self titled magazine has over 3.5 million subscribers and is read by 23 million adults each week, including over 18 million men. It was the first magazine with circulation over one million to win the...
credits Patrick Arnold
Patrick Arnold
Patrick Arnold is an American organic chemist responsible for creating the designer steroid tetrahydrogestrinone, also known as THG and "the clear". THG, along with two other anabolic steroids that Patrick Arnold manufactured , were drugs at the heart of the BALCO scandal...
for introducing androstenedione to the North American market. Andro was legal and able to be purchased over the counter and consequently it was in common use in Major League Baseball
Major League Baseball
Major League Baseball is the highest level of professional baseball in the United States and Canada, consisting of teams that play in the National League and the American League...
throughout the 1990s by record-breaking sluggers like Mark McGwire
Mark McGwire
Mark David McGwire , nicknamed "Big Mac", is an American former professional baseball player who played his major league career with the Oakland Athletics and the St. Louis Cardinals. He is currently the hitting coach for the St...
. The supplement is banned by the World Anti-Doping Agency
World Anti-Doping Agency
The World Anti-Doping Agency , , is an independent foundation created through a collective initiative led by the International Olympic Committee . It was set up on November 10, 1999 in Lausanne, Switzerland, as a result of what was called the "Declaration of Lausanne", to promote, coordinate and...
, and hence from the Olympic Games
Olympic Games
The Olympic Games is a major international event featuring summer and winter sports, in which thousands of athletes participate in a variety of competitions. The Olympic Games have come to be regarded as the world’s foremost sports competition where more than 200 nations participate...
.
The International Olympic Committee in 1997 banned androstenedione and placed it under the category of androgenic-anabolic steroids.
Androstenedione is banned by the USOC and NCA but not by MLB and the NBA.
Barry R. McCaffrey, the director of the White House's Office of National Drug Control Policy, attempted to determine whether androstenedione could be classified as an anabolic steroid in July of 1999. However, it could not because there is no proof of it promoting muscle growth.
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 steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...
s and prohormone
Prohormone
A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. The primary function of a prohormone is to enhance the strength of the hormone that already occurs in the...
s on a list of controlled substance
Controlled substance
A controlled substance is generally a drug or chemical whose manufacture, possession, or use are regulated by a government. This may include illegal drugs and prescription medications ....
s, making possession of the banned substances a federal crime. The law took effect on January 20, 2005. Surprisingly, 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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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
Military of the United States
The United States Armed Forces are the military forces of the United States. They consist of the Army, Navy, Marine Corps, Air Force, and Coast Guard.The United States has a strong tradition of civilian control of the military...
.
The Andro-Project
The "Andro-Project", conducted by medical researchers at East Tennessee State University, showed that the supplement "Andro"(androstenedione/androstenediol) does not increase muscle mass or strength.Biological effects
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 100 mg dose 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 which examined the effect of androstenedione on strength trainingStrength training
Strength training is the use of resistance to muscular contraction to build the strength, anaerobic endurance, and size of skeletal muscles. There are many different methods of strength training, the most common being the use of gravity or elastic/hydraulic forces to oppose muscle contraction...
. At dosages of 50 mg or 100 mg per day, andro 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 positive and negative 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.
Because androstenedione is converted in part to estrogens, people taking this supplement may have estrogenic side effects, although none of the studies cited above used a sufficiently high dosage to draw any conclusions.