Circadian rhythms in physiology and behavior are regulated by a master clock resident in the suprachiasmatic nucleus (SCN) of the hypothalamus, and dysfunctions in the circadian system can lead to serious health effects. This paper reviews the organization of the SCN as the brain clock, how it regulates gonadal hormone secretion, and how androgens modulate aspects of circadian behavior known to be regulated by the SCN. We show that androgen receptors are restricted to a core SCN region that receives photic input as well as afferents from arousal systems in the brain. We suggest that androgens modulate circadian behavior directly via actions on the SCN and that both androgens and estrogens modulate circadian rhythms through an indirect route, by affecting overall activity and arousal levels. Thus, this system has multiple levels of regulation; the SCN regulates circadian rhythms in gonadal hormone secretion, and hormones feed back to influence SCN functions.For optimal function, organisms and cells must locate and operate in a defined temporal and spatial niche. The need for resource partitioning is obvious in the spatial domain and is also important in the temporal domain. The daily rising and setting of the sun provides a predictable environmental time cue to which organisms are sensitive. In mammals, a master circadian clock located in the suprachiasmatic nucleus (SCN) ensures that peripheral clocks throughout the brain and body function in the appropriate phase. Entrainment (synchronization to the environment) in mammalian systems involves the resetting of this master clock, which then communicates timing information to the rest of the body. In the absence of environmental cues, the internal clock runs at its endogenous, free-running period. This system permits the prediction of environmental changes while maintaining plastic responses to changes in the environment.
SCN as Brain ClockEvidence that the SCN is the locus of a master circadian clock in mammals has been gathered over many years from many labs and entails methodologically distinct experimental paradigms with converging lines of evidence (1, 2). Briefly, lesions of the SCN result in a loss of all circadian rhythmicity in behavior and physiology, including hormone secretion. The SCN expresses rhythmic electrical and metabolic activity, even when placed in a dish in isolation from the rest of the brain (3, 4). After creation of a hypothalamic island containing the SCN, rhythmic electrical activity continues within the island (5), and hamsters bearing such hypothalamic islands continue to show rhythmic locomotor activity although the gonadal regression response to long-term constant darkness is lost (6). Transplantation of fetal hypothalamic tissue containing the SCN into the third ventricle of an SCN-lesioned animal restores circadian locomotor rhythms with a period reflecting that of the donor animal, but again, the gonadal regression response to constant darkness is lost (7,8). Interestingly, rhythms in hormone secretion are not restored by ...