Androstenol

Androstenol

Systematic (IUPAC) name
(2R,5R,7S,15R)-2,15-dimethyltetracyclo[8.7.0.02,7.011,15]heptadec-13-en-5-ol
Identifiers
ATC code	none
PubChem	CID: 101989
IUPHAR/BPS	2761
DrugBank	DB01889 Y
ChemSpider	92136 Y
ChEBI	CHEBI:40933 Y
ChEMBL	CHEMBL142348 Y
Chemical data
Formula	C19H30O
Molecular mass	274.440 g/mol
SMILES C[C@]12CC[C@H]3[C@H]([C@@H]1CC=C2)CC[C@@H]4[C@@]3(CC[C@H](C4)O)C
InChI InChI=1S/C19H30O/c1-18-9-3-4-16(18)15-6-5-13-12-14(20)7-11-19(13,2)17(15)8-10-18/h3,9,13-17,20H,4-8,10-12H2,1-2H3/t13-,14+,15-,16-,17-,18-,19-/m0/s1 Y Key:KRVXMNNRSSQZJP-PHFHYRSDSA-N Y
NY (what is this?)  (verify)

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

Androstenol, or a derivative, is found in truffles, and is offered as an explanation for how pigs locate them deep in the ground.

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 (androstadienone to androstenone), 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-like, and anticonvulsant 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 of the human menstrual cycle. In accordance, it has been proposed that androstenol may be involved in the menstrual synchrony 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, epipregnanolone, 3β-dihydroprogesterone, and 3β-androstanediol, which similarly do not act as such, in contrast to their 3α-hydroxy variants.

Androstenol, along with several isomers of androstanol, is an antagonist of the constitutive androstane receptor (CAR). Androstenol has minimal or no androgenic activity.

See also

• Androstadienol
• Androstadienone
• Androstenone
• Androsterone
• Estratetraenol
• 4,16-Androstadien-3β-ol
• 17-Phenylandrostenol