Genes and body's 24-hour clock: NIH study

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U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH NIH News

Eunice Kennedy Shriver National Institute of Child Health and Human Development

(NICHD) <http://www.nichd.nih.gov/>

For Immediate Release: Monday, March 30, 2009

 

CONTACTS: Robert Bock or Marianne Glass Miller, 301-496-5133, <e-mail:

bockr

 

GENE SCAN SHOWS BODY'S CLOCK INFLUENCES NUMEROUS PHYSICAL FUNCTIONS

From Immunity to Thyroid Hormones, Pineal Gland Exerts Effects on 600 Genes

 

The

pineal gland -- integral to setting the body's sleep and wake cycles --

may be involved in a broad range of bodily functions, according to a

study by researchers at the National Institutes of Health and other

institutions.

 

Using a technology that scans for the activity of

thousands of genes at a time, the researchers found that the activity

of  more than 600 genes in the pineal gland are synchronized in some

way with the 24-hour  sleep and wake cycle.  The genes influence such

diverse functions as inflammation and immunity. 

 

Researchers

have traditionally studied the gland in hopes of gaining insight into

the health problems of shift workers and people who frequently travel

between time zones.  The pineal gland produces the hormone melatonin,

which regulates the cycle of sleep and waking. 

 

" The results

of this study indicate that the pineal gland may be involved in a far

greater range of physiological functions than we thought, " said Duane

Alexander, M.D., director of NIH's Eunice Kennedy Shriver National

Institute of Child Health and Human Development, where much of the

research took place.  " An understanding of how the pineal gland

interacts with the genes that the researchers identified could provide

insight into a broad range of disorders and conditions. "  

 

The

study appears in the March 20, 2009 issue of The Journal of Biological

Chemistry.  The study's first author was Michael J. Bailey, of the

NICHD Section on Neuroendocrinology.  Other authors of the paper were

from the NIH Center for Information Technology, NIH's National

Institute of Mental Health, Cardiff University, Wales, the University

of Copenhagen, Denmark, King's College of London, England, and The

Genomics Institute of the Novartis Research Foundation, San Diego,

Calif.

 

The pineal gland is located within the brain, explained

the study's senior author, David Klein, Ph.D., Chief of the Section on

Neuroendocrinology.  To conduct the study, Dr. Klein and his colleagues

analyzed rodent pineal glands with a gene chip, a device that can

analyze the activity of thousands of genes at a time.  The researchers

found that the activity of 604 genes changed on a 24-hour schedule,

more than has been reported to occur in any other tissue.

 

The

researchers discovered that these genes increase their activity from 2-

to 100-fold during a 24-hour cycle.   About 70 percent of the genes

were found to increase activity at night, the remaining 30 percent

during the day. The genes are involved in a variety of functions, and

govern such processes as:

 

-- 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. 

 

" We have a long

way to go before we can fully understand the role of the pineal gland

and what makes it tick, " Dr. Klein said.  " I suspect that the pineal

gland plays a much broader role in human health than anyone has ever

imagined. "

 

This research was funded by the Intramural Research

Program of the NICHD; the Center for Information Technology;  The

Wellcome Trust;  the Biological Sciences Research Council;  the

Lundbeck Foundation; the Danish Medical Research Council; the Novo

Nordisk Foundation; the Carlsberg Foundation; the Fonden til

Lægevidenskabens Fremme; the Simon Fougner Hartmanns Familiefond; and

Pennsylvania Commonwealth Health Research Formula Funds.

 

The

NICHD sponsors research on development, before and after birth;

maternal, child, and family health; reproductive biology and population

issues; and medical rehabilitation.  For more information, visit the

Institute's Web site at <http://www.nichd.nih.gov/>.

 

The

National Institutes of Health (NIH) -- The Nation's Medical Research

Agency -- includes 27 Institutes and Centers and is a component of the

U.S. Department of Health and Human Services. It is the primary federal

agency for conducting and supporting basic, clinical and translational

medical research, and it investigates the causes, treatments, and cures

for both common and rare diseases. For more information about NIH and

its programs, visit <www.nih.gov>.

 

##

 

This NIH News Release is available online at:

<http://www.nih.gov/news/health/mar2009/nichd-30.htm>.

 

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