Control of circadian activity of birds by the interaction of melatonin with 7α-hydroxypregnenolone, a newly discovered neurosteroid stimulating locomotion

Melatonin regulates diurnal locomotor rhythms in birds as well as in other vertebrates, but the molecular mechanism by which melatonin regulates locomotor activity is poorly understood. Here, we summarize new findings showing that 7α-hydroxypregnenolone, a previously undescribed avian neurosteroid, mediates melatonin action on diurnal locomotor rhythms in birds. Recently, 7α-hydroxypregnenolone was identified as a novel avian neurosteroid in Japanese quail Coturnix japonica brain. It was found that 7α-hydroxypregnenolone acutely stimulates quail locomotor activity. Subsequently, it was clarified that diurnal changes in 7α-hydroxypregnenolone synthesis occur in parallel with changes in locomotor activity in quail. Finally, it was demonstrated that melatonin depresses the synthesis of 7α-hydroxypregnenolone, thus providing a mechanism through which the nocturnal increase in melatonin regulates diurnal changes in locomotor activity. This review highlights a novel molecular mechanism controlling circadian activity of birds by the interaction of melatonin with 7α-hydroxypregnenolone, a newly discovered neurosteroid stimulating locomotion.