Studies on neurosteroids XXVI. Fluoxetine-evoked changes in rat brain and serum levels of neuroactive androgen, 5 alpha-androstane-3 alpha,17 beta-diol.
It is well known that fluoxetine (Fluox), a selective serotonin reuptake inhibitor, increases the brain content of allopregnanolone (AP), a potent neuroactive steroid that positively modulates the action of gamma-aminobutyric acid (GABA) at the GABA type A receptors, but the influence of Fluox on the brain and serum levels of a neuroactive androgen, 5alpha-androstane-3alpha,17beta-diol (3alpha,5alpha-Adiol), is poorly understood. In this study, we examined the Fluox-evoked changes in the 3alpha,5alpha-Adiol levels and compared the level changes of 3alpha,5alpha-Adiol with those of AP. The brain and serum 3alpha,5alpha-Adiol and AP levels were determined using previously developed LC-MS/MS. The ratio of the brain 3alpha,5alpha-Adiol to the serum 3alpha,5alpha-Adiol concentrations (B/S value) was significantly elevated in the rats intraperitoneally administered Fluox (10 mg/kg). Although the magnitude of the Fluox-evoked level change in 3alpha,5alpha-Adiol was much lower than that in AP, this study demonstrated that the 3alpha,5alpha-Adiol content is also influenced by Fluox. The most probable cause for the increase in the B/S value by the Fluox treatment is the activation of the 3alpha-hydroxysteroid dehydrogenase enzyme followed by the promotion of the de novo biosynthesis of 3alpha,5alpha-Adiol in the brain.
Higashi
Tatsuya
T
University of Shizuoka, Yada, Suruga-ku, Japan. higashi@u-shizuoka-ken.ac.jp
Nagura
Yukiko
Y
Shimada
Kazutake
K
Toyo'oka
Toshimasa
T
D000728:Androgens / Q000097:blood / Q000378:metabolism; D015113:Androstane-3,17-diol / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000728:Androgens; D018377:Neurotransmitter Agents; D005473:Fluoxetine; D015113:Androstane-3,17-diol