Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an
endogenous
Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell.
For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
steroid hormone,
neurosteroid, 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 ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
with a
potency that is approximately 1/7 that of
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
.
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
An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a Chemical synapse, postsynaptic neuron less likely to generate an action potential.Purves et al. Neuroscience. 4th ed. Sunderland (MA): Sinauer Associates, Inc ...
androstane neurosteroid,
acting as a
positive allosteric modulator of the
GABAA receptor,
and possesses
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...
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 formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
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
neurosteroid 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.
Androstanediol, a metabolite of androsterone, 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 (: axillae or axillas; also known as the 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 a ...
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 many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
.
It may also be secreted by human
sebaceous gland
A sebaceous gland or oil 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 ...
s.
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 the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
. Testosterone is converted to 5α-dihydrotestosterone and
5β-dihydrotestosterone by
5α-reductase and
5β-reductase, respectively. The enzyme
3α-hydroxysteroid dehydrogenase converts the reduced forms to
3α-androstanediol and
3β-androstanediol, 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 which are then converted to androsterone and etiocholanolone by
3α-hydroxysteroid dehydrogenase and
3β-hydroxysteroid dehydrogenase, respectively.
Metabolism
Androsterone is
sulfated into
androsterone sulfate and
glucuronidated into
androsterone glucuronide and these
conjugates are
excreted in
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
.
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 Pinaceae. ''Pinus'' is the sole genus in the subfamily Pinoideae.
''World Flora Online'' accepts 134 species-rank taxa (119 species and 15 nothospecies) of pines as cu ...
pollen
Pollen is a powdery substance produced by most types of flowers of seed plants for the purpose of sexual reproduction. It consists of pollen grains (highly reduced Gametophyte#Heterospory, microgametophytes), which produce male gametes (sperm ...
, celery,
truffle
A truffle is the Sporocarp (fungi), fruiting body of a subterranean ascomycete fungus, one of the species of the genus ''Tuber (fungus), Tuber''. More than one hundred other genera of fungi are classified as truffles including ''Geopora'', ''P ...
s and is well known in many
animal
Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
species
A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
.
History
Androsterone was first isolated in 1931, by
Adolf Friedrich Johann Butenandt and
Kurt Tscherning. 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.
See also
*
Androgen backdoor pathway
*
List of androgens/anabolic steroids
*
List of neurosteroids § Androstanes
*
List of neurosteroids § Pheromones and pherines
*
3α-Hydroxysteroid dehydrogenase
References
External links
Androsterone entry in the HMDB
{{GABAA receptor positive modulators
5α-Reduced steroid metabolites
Anabolic–androgenic steroids
Androstanes
Hormones of the liver
Human metabolites
Human pheromones
Mammalian pheromones
Neurosteroids
Steroid hormones
GABAA receptor positive allosteric modulators