Media Contacts
r. Robert C. Smart, 919/515-7245
Tim Lucas, News Services, 919/515-3470 or
[email protected]
October 21, 1996
Estrogen-Blocking Compound Found to Cause Hair Growth
EMBARGOED FOR RELEASE AT 5 P.M., OCT. 28
Scientists at North Carolina State University have found that an estrogen-blocking compound used in their studies has an unexpected side effect: It induces hair growth in laboratory mice by stimulating inactive hair follicles.
Treating the mice with a biologically active estrogen was found to have the opposite effect: It blocks hair growth by locking follicles into a resting mode.
The discoveries suggest estrogen plays a much more important role in hair growth than scientists previously thought -- knowledge which ultimately could lead to new, more effective hair-loss treatments for humans.
"Our findings indicate that an estrogen receptor pathway in specific cells of the mice's hair follicles somehow acts as a switch, essentially turning on and off hair growth," says Dr. Robert C. Smart, associate professor of molecular and cellular toxicology. "It's a novel finding, because a great deal of past research (on hair loss) has focused on androgens, but not estrogens."
Smart and Hye-Sun Oh, a doctoral candidate in toxicology at NC State, made the discoveries during a three-year study that began as an investigation of the carcinogenic effects of a pesticide on mice, and of estrogen's role in the process. After links between estrogens, estrogen-receptor inhibitors and hair growth became evident, they shifted their focus to that.
Their findings will be published in the Oct. 29 issue of the
Proceedings of the National Academy of Sciences USA.
In the study, small doses of an estrogen receptor antagonist (a substance that blocks the protein interaction necessary for estrogen activity in a cell) called ICI 182,780 were applied to the skin of shaved mice twice weekly, Smart says. Tissue studies of treated hair follicles showed that hair follicle growth began within a week of the first application. "By two weeks, the visible hair growth on treated mice was about the same as on mice who had never been shaved, while mice that were not treated with ICI 182,780 grew no hair, " he says.
A patent for the use of estrogen blockers for treating hair loss and promoting hair growth has been applied for by NC State.
Smart and Oh also found that twice-weekly topical treatments of a biologically active estrogen called 17-beta-estradiol had the reverse effect -- they locked the mice's hair follicles into a resting phase and prevented hair growth for as long as treatments were continued.
No adverse side effects were observed, and the results were the same on both male and female mice, and on mice of various ages.
Whether the treatments will have similar results on humans is not yet known. Smart and Oh are now working with a dermapathologist at Wake Forest University's Bowman-Gray School of Medicine to determine if the estrogen receptor that regulates hair growth in mice also is present in man. "If it is there, then it's a good bet these treatments will have the same effect," Smart says.
If found to be safe and effective on humans, the treatments could be used for hair loss caused by chemotherapy, male pattern baldness or gradual thinning, as well as for treating hirsutism, the excessive growth of unwanted hair. Smart estimates it could take five years or more before the testing is completed and the treatments are available commercially.
A more immediate benefit, he says, is the new light the research sheds on estrogens' role in regulating the hair-growth cycle. "Hair follicles are complex, self-renewing structures composed of different types of cells. Dermal papilla cells at the base of the hair follicle have long been known to regulate the transition between the growth and resting phases of the hair- follicle cycle, but no one was exactly sure how. We didn't know what signals were given out by
these cells to trigger other cell types into proliferating and forming an active follicle. Essentially, it was a black box," he says.
Smart's research team, which includes both graduate and undergraduate students, answered part of this question by demonstrating that it is an estrogen receptor pathway, located in the nucleus of the dermal papilla cell, that regulates the growth cycle. Now, Smart says, scientists can proceed to the next level of investigation: "What are the genes involved?"
His team's findings about how estrogen regulates the follicular stem cells responsible for hair growth may also open new avenues of investigation in cancer research, Smart believes.
"Follicular stem cells may represent the precursor cells for certain skin cancers. If we can understand the nature of the signals that stimulate or inhibit their growth, we may then be able to block or interrupt the signals in abnormal cell growth," he says.
Smart and Oh's research was funded by the National Cancer Institute and the National Institute of Environmental Health Sciences. The estrogen inhibitor ICI 182,780 is produced by Zeneca Pharmaceuticals, which provided it to the NC State researchers for the study.
-- lucas --
NOTE TO EDITORS: An abstract of Smart and Oh's paper in the
Proceedings of the National Academy of Sciences follows on the next page. For a copy of their paper, contact Smart at (919) 515-7245 or Tim Lucas, at NC State University News Services, at (919) 515-3470.
"An Estrogen Receptor Pathway Regulates the Telogen-Anagen Hair Follicle Transition and Influences Epidermal Cell Proliferation"
by Hye-Sun Oh and Robert C. Smart,
North Carolina State University Department of Toxicology
Published Oct. 29, 1996, in the
Proceedings of the National Academy of Sciences USA,
Vol. 93, Issue 22
ABSTRACT: The hair follicle is a cyclic, self-renewing epidermal structure which is thought to be controlled by signals from the dermal papilla, a specialized cluster of mesenchymal cells within the dermis. Topical treatments with 17-Beta-estradiol to the clipped dorsal skin of mice arrested hair follicles in telogen and produced a profound and prolonged inhibition of hair growth, while treatment with the biologically inactive stereoisomer, 17-alpha-estradiol, did not inhibit hair growth. Topical treatments with ICI 182,780, a pure estrogen receptor antagonist, caused the hair follicles to exit telogen and enter anagen, thereby initiating hair growth. Immuno-histochemical staining for the estrogen receptor in skin revealed intense and specific staining of the nuclei of the cells of the dermal papilla. The expression of the estrogen receptor in the dermal papilla was hair cycle-dependent with the highest levels of expression associated with the telogen follicle. 17-Beta-estradiol-treated epidermis demonstrated a similar number of 5-bromo-2'-deoxyuridine (BrdUrd) S-phase cells as the control epidermis above telogen follicles; however, the number of BrdUrd S-phase basal cells in the control epidermis varied according to the phase of the cycle of the underlying hair follicles and ranged from 2.6 percent above telogen follicles to 7.0 percent above early anagen follicles. These findings indicate an estrogen receptor pathway within the dermal papilla regulates the telogen-anagen follicle transition and suggest that diffusible factors associated with the anagen follicle influence cell proliferation in the epidermis.
