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, 7 alpha- and 7 beta-hydroxypregnenolone is described. Intracerebroventricular administration of 7 alpha-hydroxypregnenolone, but not 7 beta-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 7 alpha-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 7 alpha-hydroxypregnenolone. Treatment of male quail with melatonin was found to depress the synthesis of 7 alpha-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 7 alpha-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. (C) 2009 Elsevier Inc. All rights reserved.