* inflammation (swelling)
* the immune response
* cell adhesion (how cells bind, or join together)
* the cell cycle (the reproduction and death of cells)

* the cytoskeleton (the inner structural material of cells)
* calcium metabolism
* cholesterol production
* endothelial tissue (the tissue that lines many of the body's organs and structures)
* transcription (the process by which DNA sequences are eventually converted through RNA into proteins)
* effects of the thyroid gland on the pineal gland
* cell signaling (the process through which hormones and other factors control cells)
* copper and zinc biology

"We were really surprised by what we found," Dr. Klein said. "We did not expect to find 24-hour rhythms in the functioning of so many genes."

Dr. Klein said that, as he and his coworkers expected, many of the genes active in the pineal gland are also active in the retina of the eye. The study authors cited this finding as highly compelling evidence that the pineal gland and the retina evolved from the same primitive light detecting structure. An earlier study on this possible evolutionary relationship is available at: http://www.nichd.nih.gov/news/releases/pinealgland.cfm.

The pineal gland is controlled by a brain structure known as the suprachiasmic nucleus, located at the base of the brain, Dr. Klein said. The suprachiasmatic nucleus is known as The Mind's Clock, because it coordinates body rhythms in response to changes in lighting that are detected by the eyes. The suprachiasmatic nucleus is connected to the pineal gland by nerve cells. At night, a brain chemical called norepinephrine, which transmits information through nerve cell networks, is released in the pineal gland. Norepinephrine, in turn, stimulates the production of another compound within the cells of the pineal gland, known as cyclic adenosine monophosphate (cyclic AMP). Cyclic AMP causes the pineal gland to produce melatonin.

The researchers noted that the daily changes in gene activity observed in the study were controlled by the release of norepinephrine and the increase of cyclic AMP.

"This is surprising, because we did not anticipate that the release of one molecule - norepinephrine - would be found to control the activity of hundreds of genes," Dr. Klein said. "It appears that this one signal triggers a highly complex response that is necessary for normal rhythmic function of the pineal gland."

Dr. Klein added that he and his colleagues are planning future studies to discern both how the cells of the pineal gland are controlled and how they influence the genes controlling other cellular functions.

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