It has been shown recently that androstenol and androstanol could modulate
gene expression through the nuclear orphan receptors CAR (constitutive andr
ostane receptor) and PXR (pregnane X receptor). Although, in the pig, andro
stenol is produced in high amounts and is active as a pheromone, its role i
n the human is ill defined. Androstenol possesses a structure similar to th
at of androgens, with the exception that it does not possess an oxygen at p
osition 17 that is crucial for androgenic and estrogenic activity. It has b
een shown that human and boar testis homogenates could produce androstenol,
but details of the biosynthetic pathway had not yet been elucidated. It ha
s also been shown recently that androstenol could modulate the activity of
CAR and PXR and the expression of some cytochrome P450 drug-metabolizing en
zymes. We wanted to determine the precise biosynthetic pathway of androsten
ol and other closely related steroids. Using transformed human embryonic ki
dney (HEK-293) cells that stably express 3 beta -hydroxysteroid dehydrogena
se, 5 alpha -reductase and 3 alpha -hydroxysteroid dehydrogenase, we have s
hown that these enzymes are able to efficiently transform the precursor 5,1
6-androstadien-3 beta -ol into androstenol. We thus provided evidence that
androstenol, We thus provided evidence that androstenol, the ligand for CAR
and PXR, is produced by the biosynthetic pathway of sex steroids. (C) 2001
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