FOR RELEASE: Jan. 17, 1997

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Groundhog Season Cycles Apply To Human Medicine

ITHACA, N.Y. -- Knowing why the groundhog comes out of hibernation in
early February may have more import than predicting winter's end, Cornell
University researchers have found.

Groundhogs have more dramatic annual biological rhythms than nearly all
other mammals and are a perfect animal model for studying them. In fact,
groundhogs, also known as woodchucks, may provide key clues into better
understanding cancer and cancer treatment, blood cell functions, brain
activity and mental health.

For more than 15 years, Cornell researchers have been raising the world's
only disease-free woodchucks (Marmota monax) to study hepatitis B infection
and the liver cancer it can cause. Those studies, supported by the
National Institutes of Health, have resulted in many advances in
understanding liver disease, including proof that hepatitis B virus
infection is the proximate cause of liver cancer and that immunization
against the virus can prevent liver cancer.

Recently, however, Patrick W. Concannon, Ph.D., an endocrinologist and
reproductive biologist in the Department of Physiology in Cornell's College
of Veterinary Medicine, has been focusing on the woodchuck's dramatic
seasonal cycles that profoundly alter the rodents' reproductive activity,
food intake, basal metabolism, body fat and total body weight from season
to season. During the year, for example, woodchucks vary their daily food
intake by 2,000 percent, and both their body weight and metabolic rates
increase up to 100 percent and then decline by 50 percent.

Concannon suspects that most mammals, including humans, have similar annual
cycles. These cycles, he believes, are driven by hormonal signals,
synchronized by annual changes in photoperiod, and influence functions such
as metabolism, reproduction, hair growth, fat deposition and so forth.

To better understand annual cycles and how they might affect liver and fat
metabolism, liver carcinogenesis, thyroid function, brain function and even
obesity, Concannon has been experimenting with the circannual cycle of the
woodchuck.

"The woodchuck may be the best mammalian species to study the underlying
biological mechanisms of circannual cycles because its large body size
allows collection of blood and tissue samples of adequate size, and we have
already determined the husbandry, dietary and housing conditions to
maintain it as a laboratory animal model in closed colonies with high rates
of reproduction," Concannon said. And, Cornell scientists have a head
start with their data on circannual changes in metabolic rate, thyroid
hormone activity and prolactin secretion.

Other scientists had observed that the seasonal cycles of woodchucks did
not vary when exposed to either short or long days. Concannon figured out
why.

"We have found that woodchucks have very powerful endogenous cycles,"
Concannon said. "In other words, they undergo a series of seasonal changes
which trigger one another and involve about a one-year cycle, even when
there are no light cues to entrain them to 12 months."

He also has determined that the woodchuck cycles can be influenced by
photoperiods but only if nature is mimicked more closely and the animals
are exposed each day to a slightly longer or shorter day. By exposing the
woodchucks to computer-controlled lighting, with gradually lengthening or
gradually shortening "days," Concannon has been able to entrain woodchucks
to a circannual cycle as if they were living in Australia or South America
and another group of woodchucks to an 8-month year.

Concannon's studies, which have recently been published in Biology of
Reproduction, Laboratory Animal Science and the Journal of Experimental
Zoology, have been the first to conclusively demonstrate that the
endogenous circannual cycle in these animals, and probably in all temperate
species, are entrained by photoperiods and that daily changes in light are
more critical than day length.

The endogenous cycles of the woodchuck are so strong that even in the
laboratory, where the temperature is maintained at 70 degrees year-round
with ample food and water, some woodchucks still stop eating and hibernate
because of the underlying biology of the circannual cycle, Concannon said.

"And guess when they stop hibernating? Right around Groundhog Day in early
February," he said. He suspects that their urge to hibernate is driven by
decreasing 'day-length' but that the effectiveness of short days (or even
total darkness underground) wears off over time. When that happens, the
processes are reversed, and the rodents emerge from hibernation with a very
healthy appetite and high energy, which are further stimulated by the
increasing day lengths that occur in late winter and spring.

"The implications of better understanding these circannual rhythms is very
significant for human medicine," said Concannon, who pointed out that
recent research clearly suggests that humans have circannual cycles,
although not as profound as those in the woodchuck. "These cycles include
changes in blood chemistry during the year and changes in hormone
secretion. Our cycles, like those of woodchucks, are most likely also
entrained by photoperiod, although such entrainment may be less than
precise due to our exposure to artificial lighting schedules at home, work
and play."

Concannon hopes that, by studying the profound circannual changes in body
function in the woodchuck, scientists can better understand the underlying
changes in brain chemistry, body metabolism and hormone secretion that have
evolved as part of the biology of circannual cycles and that probably exist
in most species. The woodchuck also may provide clues to the basis of
circannual changes in body function that just now are being recognized in
human clinical research. For example, there are circannual changes in the
rate of DNA synthesis and cell division in bone marrow and intestinal cells
in humans, and that has implications in the use, efficacy and side-effects
of chemotherapy used to treat cancer.

"Clinical studies of blood cells and blood components in humans have
revealed circannual changes in the volume of red blood cells, hemoglobin,
hematocrit, white blood cell function, blood clotting proteins, tumor
marking proteins in cancer patients, hormone receptors on blood cells,
blood protein levels and cholesterol levels in different blood fractions,"
Concannon said. "Human brain activities also show circannual cycles.
Circannual rhythms have been reported for the amount and percent of
REM-sleep, the brain's serotonin-neurotransmitter system, the occurrence of
migraine attacks and even the size of vasopressin-secreting neurons in the
supra chiasmatic nucleus [the nucleus that appears to control circannual
cycles]."

Mental health also has a seasonal component, as seen in the winter mental
depression of seasonal affective disorder (SAD). Those patients have
profound seasonal changes in taste sensation, appetite and food intake,
Concannon said. Normal individuals also appear to have circannual changes
in basal metabolism, energy level and appetite, as well as in metabolic
hormones like prolactin.

Concannon said that seasonal changes also occur in blood pressure, the
incidence of stroke and the secretion of kidney and adrenal hormones that
most affect blood pressure (renin and aldosterone). They also exist for the
major adrenal stress hormone (cortisol), thyroid secretion and secretion of
the pituitary hormone that controls the thyroid.

"Even reproductive function has a circannual cycle," Concannon said. "Men
have circannual rhythms in testosterone, pituitary hormones controlling
testis activity, sperm counts and semen chemistry. Circannual patterns have
been reported for the level of hormone receptors in breast cancer, for the
occurrence of premature births and for the chemistry of the fluid in
ovarian follicles."

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Woodchuck Wisdom

Groundhog Day facts about Marmota monax

Groundhog, woodchuck -- what's the difference?

Woodchuck and groundhog are common terms for the same animal, the rodent
with the scientific name of Marmota monax. Most closely related to
squirrels, woodchucks actually can climb trees and also swim. But they are
more likely to be found in or around burrows that they excavate -- often at
the edge of wooded areas. Their natural range stretches from southern
Alaska to northern Georgia. For a wild woodchuck, "old" is around 6 years;
in captivity, woodchucks can live 10-12 years. The average litter size is
four pups, born in April or early May. By June, they are weaned and set off
to establish their own burrows.

What's so special about Feb. 2?

Celestially speaking, Groundhog Day on Feb. 2 is a "cross-quarter" day,
about halfway between the winter solstice in December and the vernal
equinox in March, and is celebrated in some cultures as the midpoint of
winter. It's not far from the time many groundhogs end their hibernation
anyway, around the second week of February.

Who doesn't like woodchucks?

Their natural enemies are foxes and coyotes. Farmers destroy some because
woodchuck burrows disrupt agriculture and endanger livestock. Others
succumb to highway traffic or to parasitic diseases of the nervous system.
Freshly excavated dirt is a sign of an occupied burrow, although the
animals often maintain secretive "plunge holes" for a quick escape.
Groundhogs show their affection by rubbing cheeks, where their scent glands
are located.

What's going on in that woodchuck burrow?