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

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 coin ...

, and putative pheromone. It is a weak androgen with a potency that is approximately 1/7 that of testosterone. 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, c ...

of testosterone and dihydrotestosterone (DHT). In addition, it can be converted back into DHT via 3α-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, bypassing conventional intermediates such as androstanedione 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

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

is epiandrosterone, and its 5β- epimer 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 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 supe ...

and skin as well as in the urine. It may also be secreted by human sebaceous glands. It is described as having a musky odor similar to that of androstenol. 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. 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 bo ...

by 5α-reductase 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 ( ...

, which are subsequently converted by 17β-hydroxysteroid dehydrogenase to androsterone and etiocholanolone, respectively. Androsterone and etiocholanolone can also be formed from androstenedione via the action of 5α-reductase and 5β-reductase forming 5α-androstanedione and

5β-androstanedione Etiocholanedione, also known as 5β-androstanedione or as etiocholane-3,17-dione, is a naturally occurring etiocholane (5β-androstane) steroid and an endogenous metabolite of androgens like testosterone, dihydrotestosterone, dehydroepiandrosteron ...

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 and glucuronidated into androsterone glucuronide and these conjugates are excreted in urine.

Chemistry

Sources

Androsterone has been shown to naturally occur in pine

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 gametophyt ...

, celery, truffles and is well known in many

animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...

species In biology, a species is the basic unit of Taxonomy (biology), 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 ...

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.

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