Androstenol, also known as 5α-androst-16-en-3α-ol (shortened to 3α,5α-androstenol or 3α-androstenol), is a 16-androstene class

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 a ...

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 ...

and

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 ...

in humans and other mammals, notably pigs. It possesses a characteristic musk-like odor. Androstenol, or a derivative, is found in

black truffles ''Tuber melanosporum'', called the black truffle, Périgord truffle or French black truffle, is a species of truffle native to Southern Europe. It is one of the most expensive edible mushrooms in the world. Taxonomy Italian naturalist Carlo Vi ...

. This was offered as an explanation for how pigs locate them deep in the ground: Androstenol is produced in the saliva of male pigs. However, experiments in France using pigs to scent truffles, truffle scent extract, and purified androstenol showed that pigs responded to the first two (actually trying to eat dirt containing the truffle extract), but ignored the androstenol. A positional isomer of androstenol, 3β-androstenol (5α-androst-16-en-3β-ol), is also endogenous to humans (as well as to pigs), behaving as a pheromone and contributing to axillary odor.

Biosynthesis

In humans and boars, androstenol is biosynthesized in the testes. Pregnenolone is metabolized into androstadienol by the 16-ene-synthetase activity of CYP17A1. Androstadienol is then sequentially converted into androstenol by 3β-hydroxysteroid dehydrogenase ( androstadienol to androstadienone),

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 of ...

(androstadienone to

androstenone Androstenone (5α-androst-16-en-3-one) is a 16-androstene class steroidal pheromone. It is found in boar's saliva, celery cytoplasm, and truffle fungus. Androstenone was the first mammalian pheromone to be identified. It is found in high concent ...

), and 3α-hydroxysteroid dehydrogenase (androstenone to androstenol), in a manner analogous to the biosynthesis of 3α-androstanediol from dehydroepiandrosterone (DHEA). Androstenol may also be synthesized in the adrenal glands and the ovaries in humans. In addition, androstenol may be synthesized in the human nasal mucosa from androstenone, and likely also from androstadienol and androstadienone in this area.

Distribution

Considerable amounts of androstenol are present in human urine, and it is also present in the blood plasma and saliva of humans and pigs as well as in the axillary sweat of humans. Due to its ability to cross the blood-brain-barrier, androstenol is likely present in the central nervous system as well.

Biological activity

Androstenol, similarly to the related endogenous steroids 3α-androstanediol and androsterone, has been found to act as a potent positive allosteric modulator of the GABA_A. It has been proposed that this action may mediate the pheromone effects of androstenol. Moreover, as androstadienol, androstadienone, and androstenone are all converted into androstenol, it could mediate their pheromone effects as well. In animals, androstenol has been found to produce anxiolytic-like,

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

-like, and

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 b ...

effects. Androstenol has also been found to modify the behavioral and social responses of humans. In addition, androstenol has been found to decrease luteinizing hormone (LH) pulse frequency during the

follicular phase The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle (or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a ful ...

of the human

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

. In accordance, it has been proposed that androstenol may be involved in the

menstrual synchrony Menstrual synchrony, also called the McClintock effect, or the Wellesley effect, is a contested process whereby women who begin living together in close proximity would experience their menstrual cycle onsets (the onset of menstruation or menses) ...

of women. In contrast to androstenol (3α-androstenol), its 3β-epimer, 3β-androstenol, does not potentiate the GABA_A receptor, even at high concentrations. This is in accordance with other 3β-hydroxy steroids, including

isopregnanolone Isopregnanolone, also known as isoallopregnanolone and epiallopregnanolone, as well as sepranolone (), and as 3β-hydroxy-5α-pregnan-20-one or 3β,5α-tetrahydroprogesterone (3β,5α-THP), is an endogenous neurosteroid and a natural 3β-epimer of ...

epipregnanolone Epipregnanolone, also known as 3β-hydroxy-5β-pregnan-20-one, 3β,5β-tetrahydroprogesterone, or 3β,5β-THP, is an endogenous neurosteroid. It acts as a negative allosteric modulator of the GABAA receptor and reverses the effects of potentiato ...

3β-dihydroprogesterone 3β-Dihydroprogesterone (3β-DHP), also known as 3β-hydroxyprogesterone, or pregn-4-en-3β-ol-20-one (4-pregnenolone, δ4-pregnenolone), is an endogenous steroid. It is biosynthesized by 3β-hydroxysteroid dehydrogenase from progesterone. Un ...

, 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 similarly do not act as such, in contrast to their 3α-hydroxy variants. Androstenol, along with several isomers of androstanol, is an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of the

constitutive androstane receptor The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the ''NR1I3'' gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X ...

(CAR). Androstenol has minimal or no androgenic activity.

References

{{Xenobiotic-sensing receptor modulators Androstanes Cyclopentenes GABAA receptor positive allosteric modulators Human pheromones Mammalian pheromones Neurosteroids

Biosynthesis

Distribution

Biological activity

See also

References