Discovery of a novel avian neurosteroid, 7α-hydroxypregnenolone, and its role in the regulation of the diurnal rhythm of locomotor activity in Japanese quail

The discovery of two novel avian neurosteroids in the quail brain, 7α- and 7β-hydroxypregnenolone is described. Intracerebroventricular administration of 7α-hydroxypregnenolone, but not 7β-hydroxypregnenolone was found to stimulate locomotor activity of male quail when spontaneous nocturnal activity is low. Diurnal changes in locomotor activity in male quail were found to be correlated with a diurnal change in the concentration of diencephalic 7α-hydroxypregnenolone. This correlation was a not seen in female quail which have a lower amplitude diurnal rhythm of locomotor activity and lower daytime concentrations of diencephalic 7α-hydroxypregnenolone. Treatment of male quail with melatonin was found to depress the synthesis of 7α-hydroxypregnenolone in the diencephalon. This is a previously undescribed role for melatonin in the regulation of neurosteroid synthesis in the brain of any vertebrate. We therefore deduced in male quail, that the nocturnal depression in locomotory activity is a consequence of a depression in diencephalic 7α-hydroxypregnenolone resulting from the inhibitory action of the nocturnal increase in melatonin. This observation may be of widespread significance for the molecular control of rhythmic locomotor activity in all vertebrates.