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His findings are especially timely
because of recent federal concern about the risks of hormone
replacement therapy (HRT). That therapy, which has involved a
combination of the hormones estrogen and progestin, provides some
protection from bone fractures in women but increases women's risk
for breast cancer, uterine cancer, heart attack, stroke, and blood
clots.
The UAMS researchers found that
estren reverses loss in bone mass and strength that occurs after
menopause in women. They propose in Science that the drug
merits more study as an alternative to hormone replacement for the
purpose of preventing osteoporosis. (The article, "Reversal
of Bone Loss in Mice by Nongenotropic Signaling of Sex
Steroids," is available to subscribers at Science.)
The new drug may also be beneficial
for preventing bone loss in men.
"It's very exciting that this
may be a gender-neutral therapy. This is a brand new page of
pharmacology," Dr. Manolagas commented recently.
Hormones like estrogen operate in
two ways in the body, launching separate cascades of signals, Dr.
Manolagas and his colleagues have found in previous studies. The
so-called "genotropic" signaling pathway regulates the
expression of genes in the cell nucleus. This pathway has been
linked to cancer development in reproductive tissues. The
"non-genotropic" pathway promotes bone growth by
extending the lives of bone-building cells, called osteoblasts,
and shortening the lives of bone-destroying cells called
osteoclasts.
Dr. Manolagas and his colleagues at
UAMS and CAVHS in Little Rock tested estren in mice to see if it
could activate only the non-genotropic pathway. Estren belongs to
a group of compounds called "ANGELS," for Activators of
Non-Genomic Estrogen-Like Signaling.
The article in Science
follows the UAMS group's earlier report in the journal Cell
in March 2001.
Dr. Manolagas is director of the
Division of Endocrinology in the Department of Internal Medicine
of the UAMS College of Medicine and chief of the section of
endocrinology at the Central Arkansas Veterans Healthcare System.
He directs the UAMS Center for Osteoporosis and Metabolic Bone
Diseases.
His colleagues in the study are S.
Kousteni, J-R. Chen, T. Bellido, L. Han, A.A. Ali, C.A. O'Brien,
L. Plotkin, Q. Fu, A.T. Mancino, Y. Wen, A.M. Vertino, C.C.
Powers, S.A. Stewart, R. Ebert, A.M. Parfitt, R.S. Weinstein, and
R.L. Jilka.
The UAMS research team recently
made the greatest number of oral presentations of any national or
international group at the annual meeting of the American Society
for Bone and Mineral Research. The group delivered 12
presentations at the meeting in San Antonio, Texas, Sept. 20-24.
Two members, Lilian Plotkin, Ph.D., and Jin Ran Chen, M.D., PH.D.,
received "young investigator" awards at the conference.
Scientists with the center at UAMS have been among the busiest
presenters at the annual scientific meeting for each of the last
10 years.
Dr. Manolagas received his
doctorate of medicine from the University of Athens Medical School
in Athens, Greece. He served his residency at Stepping Hill
Hospital in Stockport, England, and was a fellow in endocrinology
at Manchester Royal Infirmary, University of Manchester, England.
Prior to his present position, he was on the faculty of the
University of California at San Diego for nine years, and Indiana
University for six years.
Author of more than 200 articles
and book chapters, and more than 300 abstracts, Dr. Manolagas has
conducted research on the pathophysiology of osteoporosis and
other disorders of bone and mineral metabolism, and the
interactions of the endocrine and the immune system.
He is a member of the highly
prestigious Association of American Physicians, the recipient of
the Founder's award of the American Society for Bone and Mineral
research for his fundamental contributions to the field, the
winner (among 52 contestants across the nation) of the highly
prestigious AlliedSignal award for research on aging for studies
on the new drugs in 1999, and the UAMS Distinguished Faculty
Scholar in 2000.
The study was funded by the
National Institutes of Health, the Department of Veterans Affairs,
and Anabonix, Inc., which has a licensing agreement with UAMS,
through the business accelerator UAMS Arkansas BioVentures, to
develop and commercialize anabolic drugs, including estren, for
osteoporosis.
# # #
Contact:
Elizabeth F. Shores
501-686-8394
ShoresElizabethF@uams.edu
UAMS
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