Biological - NIH Office of Science Education - National Institutes of ...

Sleep, Sleep Disorders, and Biological Rhythms
rises in the biological daytime. This fluctuation
persists even in the absence of sleep. Activity during
the day and sleep during the night reinforce
this cycle of changes in body temperature, as seen
in Figure 9.
Figure 9. Body temperature in relation to the sleep
cycle.
The release of melatonin, a hormone produced by
the pineal gland, is controlled by the circadian
clock in the SCN. Its levels rise during the night
and decline at dawn in both nocturnal and diurnal
species. Melatonin has been called the hormone of
darkness because of this pattern. The SCN controls
the timing of melatonin release; melatonin then
feeds back on the SCN to regulate its activity. In
mammals, for example, most of the brain receptors
for melatonin are located in the SCN. Research has
demonstrated that administering melatonin can
produce shifts in circadian rhythms in a number of
species including rats, sheep, lizards, birds, and
humans. These effects are most clearly evident
when melatonin is given in the absence of light
input. Thus, for example, giving melatonin to
blind people can help set their biological clocks.
Melatonin is available as an over-the-counter
nutritional supplement. Although claims are made
that the supplement promotes sleep, the evidence
for this is inconclusive. Potential side effects of
long-term administration of melatonin remain
unknown, and its unsupervised use by the general
public is discouraged.
In addition to synchronizing these daily rhythms,
biological clocks can affect rhythms that are
longer than 24 hours, especially seasonal
rhythms. Some vertebrates have reproductive systems
that are sensitive to day length. These animals
can sense changes in day length by the
amount of melatonin secreted. The short days and
long nights of winter turn off the reproductive
systems of hamsters, while in sheep the opposite
occurs. The high levels of melatonin that inhibit
reproduction in hamsters stimulate the reproductive
systems of sheep, so they breed in winter and
give birth in the spring.
Biological clocks exist in a wide range of organisms,
from cyanobacteria (blue-green algae) to
humans. Clocks enable organisms to adapt to
their surroundings. Although scientists currently
believe that clocks arose through independent
evolution and may use different clock proteins,
they all share several regulatory characteristics. In
particular, they are maintained by a biochemical
process known as a negative feedback loop.
Much of what is known about clock regulation has
come from studying the fruit fly Drosophila
melanogaster, from which biological clock genes
were first cloned. Two genes called period (per) and
timeless (tim) were found to cycle with a 24-hour,
or circadian, rhythm. 8, 12 The genes are active early
in the night and produce mRNA that is then translated
into the proteins PER and TIM. These proteins
begin to accumulate in the cytoplasm. After
the proteins have reached high enough levels, PER
protein binds to TIM protein, forming a complex
that enters the cell’s nucleus. In the nucleus, the
PER-TIM complexes bind to the per and tim genes
to suppress further transcription. This creates what
is called a negative feedback loop. After a while, the
PER and TIM proteins degrade, and transcription
from the per and tim genes begins again.
This description of Drosophila’s clock is a simplified
one. Other genes have been identified that
produce proteins involved with regulating the circadian
clock. For example, the proteins CLOCK,
CYCLE, and VRILLE are transcription factors that
regulate expression of the per and tim genes. Other
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