The signal to get up
If someone tiptoes into your room in the middle of the night and turns on the light, your brain automatically flips its own switch - and quickly cuts down on production of melatonin, a hormone that helps us stay asleep. According to new studies, the brain goes one step further and destroys the melatonin that is already there. Bright light causes a simultaneous drop in both melatonin levels and the activity of the enzyme needed to synthesize melatonin: N-acetyltransferase (AA-NAT). Normally, cells use protein inhibitors to turn off enzymes. In AA-NAT, however, there has been no evidence of this type of inhibition. To find out what forces are at work in the enzyme, David Klein and his colleagues at the National Institute of Child He alth and Human Development in Bethesda, Maryland, developed a sensitive antibody test that can measure the amount of AA-NAT in a tissue sample (Science 01 27February 1998).
The researchers used this test on rats. After shining a bright light on a sleeping rat for 15 minutes in the middle of the night, they found that the level of AA-NAT in the brain's pineal gland - which secretes melatonin - had fallen by a hundredfold and was barely detectable. Then the scientists inhibited the protein complexes in the cell known as proteasomes, which cut up proteins, and the normal AA-NAT nocturnal values suddenly returned. This suggests that the level of acetyltransferase is actually controlled by the proteasome.
The rapid destruction "tells us how important it is that melatonin is gone when exposed to light," says Al Lewy, a chronobiologist at Oregon He alth Sciences University in Portland. According to Lewy, the brain wouldn't want melatonin to work during the day because the hormone would mess up the body's internal clock."Now we know that we have to find out what blocks or enhances AA-NAT destruction by the proteasomes," explains Klein. "If we can do that, we can change the melatonin levels."
With the right medication, for example, workers could work night shifts more easily.