Endocrine Abstracts

In mammals, a master pacemaker residing in the hypothalamic suprachiasmatic nuclei (SCN) and subordinate clocks found throughout the body coordinate circadian rhythms of behavior and physiology. One prominent physiological rhythm is the release of glucocorticoids (GCs) by the adrenal gland, brought about by the rhythmic activation of the hypothalamus–pituitary–adrenal (hpa) axis and the secretion of ACTH from the pituitary. In humans, blood GC levels peak in the early morning while nocturnal rodents show highest secretion rates in the evening, coinciding with the beginning of the active phase in both species.

We have characterized a peripheral circadian clock residing in the outer cortical layers of the murine adrenal. Rhythmic activation of several core clock genes and of hundreds of clock controlled genes was detected, indicating a role of the adrenal clock in regulating gluco- and mineral corticoid biogenesis. In mice with a genetic disruption of the circadian system, hpa axis regulation is defective. Organ culture and tissue transplantation experiments suggest that the adrenal clock gates GC production in response to ACTH. These data are supported by transcriptome analyses, identifying a number of clock-controlled regulators of the steroidogenic machinery.

In vivo the adrenal circadian clock can be directly – and independently of the SCN pacemaker – entrained by light, and drive GC release rhythms in the absence of a rhythmic ACTH signal. When internal synchrony is disrupted, e.g. by repetitive night shifts or after long distance travels (jet lag), the adrenal clock regulates the adaptation of physiological and behavioral rhythms. Pharmacological manipulation of GC rhythms modifies behavioral re-entrainment during jet lag and, thus, might provide a new target for the alleviation of the numerous physiological and psychological symptoms classified as the jet lag syndrome.