Abstract
Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7α-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507α and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7α-hydroxypregnenolone was demonstrated. 7α-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7α-hydroxypregnenolone in the regulation of locomotor activity, diurnal, and seasonal changes in 7α-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7α-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7α-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7α-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7α-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.
Highlights
The brain has traditionally been considered as a target site for peripheral steroid hormones
Similar seasonal changes in the expression of cytochrome P4507α occurred in the male brain (Haraguchi et al, 2010). These findings suggest that the increase in locomotor activity of male newts in the spring breeding period can be accounted for an increase in 7α-hydroxypregnenolone synthesis in the brain
REGULATORY MECHANISMS OF SEASONAL CHANGES IN 7α-HYDROXYPREGNENOLONE SYNTHESIS AND ACTION Plasma prolactin (PRL) levels in the male newt are elevated during the breeding period (Matsuda et al, 1990; Mosconi et al, 1994) and it has been shown that PRL acts directly on the brain to regulate courtship behavior in the male newt (Toyoda et al, 2005)
Summary
The brain has traditionally been considered as a target site for peripheral steroid hormones. 7α-Hydroxypregnenolone synthesis in the brain of male newts showed marked changes during the annual breeding cycle, with a maximum level in the spring breeding period when locomotor activity of wild populations of the same species increases (Matsunaga et al, 2004). Administration of 7α-hydroxypregnenolone acutely increases locomotor activity of male newts in the non-breeding period when endogenous 7α-hydroxypregnenolone synthesis in the brain is low (Matsunaga et al, 2004).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
