CONTACT: BECKY SOGLIN
Iowa City IA 52242
(319) 335-6660; fax (319) 384-4638
Release: June 11, 2002
UI study sheds light on how the hormone DHEA affects cells
A major stumbling block to understanding how dehydroepiandrosterone (DHEA)
affects the body has been the lack of a clearly identifiable mechanism of
how the hormone, often touted as the "fountain of youth," acts on
However, a University of Iowa Health Care study is the first to show evidence
of a cellular receptor through which DHEA stimulates production of nitric
oxide, a chemical that helps regulate blood pressure, inhibits blood clotting
and prevents narrowing of the arteries. The findings, which appear in the
June 14 issue of the Journal of Biological Chemistry, may help investigators
design clinical trials of DHEA, which have been few.
"The significance of our study is that it provides a scientific basis
for further study of the DHEA action in humans," said the study's lead
investigator Joseph Dillon, M.D., UI assistant professor of internal medicine
and a researcher and staff physician with the Veterans Affairs Medical Center
in Iowa City. "Our findings show that there is a receptor for DHEA on
the inner lining cells of blood vessels. The receptor responds to levels of
DHEA that circulate normally within the blood stream and links DHEA to the
production of nitric oxide. Unlike research with all the other major hormones
and steroids, no one had previously been able to identify a receptor for DHEA
DHEA and a closely related molecule called DHEAS are made mainly in the
adrenal gland and circulate in the blood stream in higher concentrations than
any other steroid hormone, including estrogen or testosterone. DHEA production
increases around age 6 and peaks in the mid-20s.
A 75-year old person has about 20 percent of the amount of DHEA in circulation
that he or she had at age 25. Some older people take DHEA supplements, which
are available without a physician's prescription.
Dillon, whose co-investigator was Dongmin Liu, Ph.D., a UI research investigator,
said their strategy was to look in an unusual place for the receptor.
"All steroid hormones have receptors within cells. The hormone enters
the cell and then turns on the receptor," Dillon explained. "We
found the DHEA receptor on the outside, not inside, of cells.
We also looked at cells which have not previously been examined. Other investigators
have focused their research on immune blood cells or the liver, but we looked
at the endothelium, or cells lining the blood vessels."
It appears Dillon's findings have made a substantial contribution to begin
to figure out the DHEA biological puzzle, said Frank Bellino, Ph.D., administrator
of the Endocrinology Program within the Biology of Aging Program at the National
Institute on Aging (NIA), which provided funding for the study.
"I think this is the first paper with apparently reasonably firm evidence
that DHEA interacts with G-protein coupled receptors, a class that people
have not previously investigated," Bellino said. "Knowing the biological
pathway through which DHEA may act will help in designing better clinical
Bellino emphasized that Dillon's findings do not reveal whether there are
benefits to taking DHEA but provide a firm starting point for conducting studies
to sort out risks and benefits. The NIA currently does not recommend that
people take DHEA because of the lack of evidence of any benefits.
"There is the issue of exaggerated claims -- that the DHEA stops cancer
and prevents diabetes and obesity -- and these claims are based on rodent
research. However, the biology of DHEA is very different in rodents than it
is in humans," Bellino said. "Rodents are not a good model for humans
when it comes to DHEA. They make it differently and at much lower levels."
The Food and Drug Administration does not currently regulate DHEA because
of its status as a dietary supplement.
Dillon said the next steps in his research will be to define all the cellular
steps involved in how DHEA and closely related steroids produce their effects.
"We can now start to tease apart the effects of DHEA that definitely
can be attributed to a specific mechanism," he said. "Once we have
fully isolated the receptor, we will be able to determine if there are DHEA
steroid products that are even more powerful than DHEA itself.
"Completing the isolation of the receptor will help us to rapidly test
novel compounds and other natural hormonal products of DHEA in order to eventually
develop medications that have beneficial effects in a wide range of diseases,
including cancer, heart disease, obesity and diabetes," Dillon added.
In addition to receiving National Institute on Aging funding, the investigation
also was facilitated by the Office of Research at the Veterans Affairs Medical
Center in Iowa City.
University of Iowa Health Care describes the partnership between the
UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics
and the patient care, medical education and research programs and services
they provide. Visit UI Health Care online at www.uihealthcare.com.