Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

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 ...

neurosteroid Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was co ...

, and putative

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

. It is a 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 ...

with a

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

that is approximately 1/7 that 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 ...

. Androsterone is a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

of testosterone and

dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues includi ...

(DHT). In addition, it can be converted back into DHT via 3α-hydroxysteroid dehydrogenase and

17β-hydroxysteroid dehydrogenase A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol. See ...

, bypassing conventional intermediates such as

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), dehydroepian ...

and testosterone, and as such, can be considered to be a metabolic intermediate in its own right. Androsterone is also known to be an inhibitory

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 ...

, acting as a positive allosteric modulator of the GABA_A receptor, and possesses

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

effects. The unnatural enantiomer of androsterone is more potent as a positive allosteric modulator of GABA_A receptors and as an anticonvulsant than the natural form. Androsterone's 3β-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

epiandrosterone Epiandrosterone, or isoandrosterone, also known as 3β-androsterone, 3β-hydroxy-5α-androstan-17-one, or 5α-androstan-3β-ol-17-one, is a steroid hormone with weak androgenic activity. It is a metabolite of testosterone and dihydrotestosterone ...

, and its 5β-

epimer In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization is ...

is etiocholanolone. The 3β,5β-isomer is epietiocholanolone.

Biological function

Androsterone has generally been considered to be an inactive metabolite of testosterone, which when conjugated by glucuronidation and sulfation allows testosterone to be removed from the body, but it is a weak

that can cross into the brain and could have effects on brain function. The view of androsterone as generally being of low significance however, seems to need review in the light of 21st century research, which suggests that androsterone significantly affects

masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...

in mammalian fetuses. Masculinization of the external genitalia in humans is subject to dihydrotestosterone (DHT) derived via the recognised androgenic pathway and also via a backdoor pathway. Therefore, androstanediol can be used a marker of the backdoor pathway of DHT synthesis. Spectrometric studies identify androsterone as the main backdoor androgen in the human male fetus. Circulating levels are sex dependent, DHT being essentially absent in the female, in which titres of backdoor intermediates also are very low. In males, backdoor intermediates occur mainly in the liver and adrenal of the fetus, and in the placenta — hardly at all in the testis. Instead, progesterone in the placenta is the main backdoor substrate for androgen synthesis. This also is consistent with the observation that placental insufficiency has been associated with disruptions of development of fetal genitalia.

Pheromone

Androsterone is found in the human

axilla The axilla (also, armpit, underarm or oxter) is the area on the human body directly under the shoulder joint. It includes the axillary space, an anatomical space within the shoulder girdle between the arm and the thoracic cage, bounded superior ...

and

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

as well as in the

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra. Cellul ...

. It may also be secreted by human

sebaceous gland A sebaceous gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest n ...

s. It is described as having a musky odor similar to that of

androstenol Androstenol, also known as 5α-androst-16-en-3α-ol (shortened to 3α,5α-androstenol or 3α-androstenol), is a 16-androstene class steroidal pheromone and neurosteroid in humans and other mammals, notably pigs. It possesses a characteristic musk ...

. Androsterone has been found to affect human behavior when smelled.

Biochemistry

Biosynthesis

Androsterone and its 5β-isomer, etiocholanolone, are produced in the body as metabolites of

. Testosterone is converted to 5α-dihydrotestosterone and

5β-dihydrotestosterone 5β-Dihydrotestosterone (5β-DHT), also known as 5β-androstan-17β-ol-3-one or as etiocholan-17β-ol-3-one, is an etiocholane (5β-androstane) steroid as well as an inactive metabolite of testosterone formed by 5β-reductase in the liver and b ...

5α-reductase 5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes o ...

and 5β-reductase, respectively. The enzyme 3α-hydroxysteroid dehydrogenase converts the reduced forms to 3α-androstanediol 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) ...

, which are subsequently converted by

to androsterone and etiocholanolone, respectively. Androsterone and etiocholanolone can also be formed from

androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-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 dehy ...

via the action of 5α-reductase and 5β-reductase forming

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 ...

and 5β-androstanedione which are then converted to androsterone and etiocholanolone by 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.

Metabolism

Androsterone is

sulfated Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

into

androsterone sulfate Androsterone sulfate, also known as 3α-hydroxy-5α-androstan-17-one 3α-sulfate, is an endogenous, naturally occurring steroid and one of the major urinary metabolites of androgens. It is a steroid sulfate which is formed from sulfation of andr ...

and glucuronidated into

androsterone glucuronide Androsterone glucuronide (ADT-G) is a major circulating and urinary metabolite of testosterone and dihydrotestosterone (DHT). It accounts for 93% of total androgen glucuronides in women. ADT-G is formed from androsterone by UDP-glucuronosyltrans ...

and these conjugates are excreted in

Chemistry

Sources

Androsterone has been shown to naturally occur in

pine A pine is any conifer tree or shrub in the genus ''Pinus'' () of the family (biology), family Pinaceae. ''Pinus'' is the sole genus in the subfamily Pinoideae. The World Flora Online created by the Royal Botanic Gardens, Kew and Missouri Botanic ...

pollen Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametop ...

, celery,

truffle A truffle is the fruiting body of a subterranean ascomycete fungus, predominantly one of the many species of the genus ''Tuber''. In addition to ''Tuber'', many other genera of fungi are classified as truffles including '' Geopora'', '' Pe ...

s and is well known in many

animal Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage ...

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...

History

Androsterone was first isolated in 1931, by Adolf Friedrich Johann Butenandt and

Kurt Tscherning Kurt is a male given name of Germanic or Turkish origin. ''Kurt'' or ''Curt'' originated as short forms of the Germanic Conrad, depending on geographical usage, with meanings including counselor or advisor. In Turkish, Kurt means "Wolf" and is ...

. They distilled over of male urine, from which they got of crystalline androsterone, which was sufficient to find that the chemical formula was very similar to

estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...

References

External links

Androsterone entry in the HMDB
{{GABAA receptor positive modulators 5α-Reduced steroid metabolites Androgens and anabolic steroids Androstanes Hormones of the liver Human metabolites Human pheromones Mammalian pheromones Neurosteroids Steroid hormones GABAA receptor positive allosteric modulators World Anti-Doping Agency prohibited substances