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Brain and Pineal 7α-Hydroxypregnenolone Regulating Locomotor Behavior: Discovery, Progress and Prospect

Author(s): Kazuyoshi Tsutsui, Shogo Haraguchi and Takayoshi Ubuka

The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. The formation of neurosteroids in the brain is a conserved property across vertebrates, but it is still incompletely elucidated in vertebrates. In fact, 7α-hydroxypregnenolone (7α-OH PREG) was identified as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates. Subsequently, the mode of action of 7α-OH PREG and the regulation of 7α-OH PREG synthesis in the brain have demonstrated by follow-up studies. Recently, it has been demonstrated that the pineal gland, an endocrine organ located close to the brain, is a major site of formation of bioactive neurosteroids. This is a new finding of the formation of neurosteroids because for a long time neurosteroids are believed to be produced in neurons and glial cells in the brain. In addition to the brain, the pineal gland actively produces 7α-OH PREG as a major pineal neurosteroid that acts on the brain to regulate locomotor rhythms. Thus, the discovery of 7α-OH PREG, a new bioactive neurosteroid, has provided a novel direction to investigate neurosteroid regulation of locomotor behavior. This review summarizes the discovery, progress and prospect of brain and pineal 7α-OH PREG regulating locomotor behavior in vertebrates.

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