Fig. 2: Concept of endocrine regulation of circadian rhythms.

Hormones can act as rhythm drivers, zeitgebers, or tuners. The function as rhythm driver is clock-independent and requires a rhythmic hormone that can influence rhythmic gene expression via direct hormone-target interactions. As a zeitgeber, hormones directly regulate clock gene expression in target tissues and can shift the phase of the clock. As a tuner, the hormonal signal is tonic but able to modulate the rhythmic reception and response to other external stimuli in the target tissue. In this way, a tonic action on the target tissue can modulate gene expression rhythms, thus eliciting a phasic response.