The circadian clock is phase delayed or advanced by light when given at early or late night, respectively. Despite the importance of the time-of-day-dependent phase-responses to light, the underlying molecular mechanism is poorly understood. Here we found that SREBP transcription factor, which regulates a large group of cholesterol biosynthetic genes, activated transcription of E4bp4, a key regulator in the phase-delaying mechanism of the chicken pineal clock, in response to a light pulse given at early night. Furthermore, we revealed that light-activated SREBP stimulated production and release of a neurosteroid 7α-hydroxypregnenolone in the pineal gland, resulting in the activation of locomotor activities of chicks. These results demonstrate a novel endocrine function of the pineal gland, which has been known to release sleep-related hormone melatonin.

Program member
Yoshitaka Fukada (Department of Cell Biology and Anatomy, Graduate School of Medicine)