Oct. 12, 1998 LA JOLLA, CALIF. -- The first steroid hormone unearthed in 30 years is chemical cousin to the molecule that lures pigs to truffles, and like that rare and elusive fungus, it is in a class by itself.
Previously discovered steroid hormones boost or turn on genes. The new hormone, described in the Oct. 8 issue of Nature, defines a tantalizing new mode of action since it is the first hormone that reverses or halts gene activity.
The study's lead author, Barry Forman, M.D., of the City of Hope Diabetes Center and formerly of The Salk Institute, along with colleagues at Salk and Baylor College of Medicine, have demonstrated that the hormone, androstanol, interacts with a receptor protein called CAR-beta. This protein normally binds to genes and stimulates their activity but, when bound by androstanol, acts as a switch to turn genes off.
Like its fungal counterpart that gives truffling pigs pause, "androstanol seems to stop gene activity in its tracks," according to co-author Ron Evans, Salk Professor and Howard Hughes Medical Institute investigator.
Androstanol is chemically related to androgen, a hormone that stimulates normal development of male sex organs and, in humans, affect secondary sex characteristics including hair loss and aggressive behavior. In some studies, androstanol appears to be a pheromone that enhances men's attractiveness to women.
"At this time, however, we have no evidence for CAR-beta being a pheromone receptor. Because androgens are involved in complex behavior and physiological responses, we do not yet know where CAR-beta fits in the grand scheme," said Evans. "The discovery of a new receptor clearly reveals the existence of a new pathway and provides a precise way to attack the problem."
The equivalent of androstanol in plants, including truffles, is androstenedione, the nutraceutical that gained notoriety for its use by Mark McGwire, who set a new home run record this summer for the St. Louis Cardinals. In the current study, androstenedione was a very weak activator of the androgen receptor "and thus how it might work remains unclear," said Evans. "Mostly this work reinforces the idea that sex steroids contribute in complex ways to human behavior and disease. This gives us one of the first new tools in decades to address these problems."
Senior author on the study is David D. Moore of Baylor College of Medicine. Other co-investigators include Iphigenia Tzameli of Baylor;
Jasmine Chen of City of Hope; Hueng-Sik Choi of the Chonnam National University, Kwangju, Republic of Korea; Devendranath Simha of Massachusetts General Hospital; and Wongi Seol of Dana-Farber Cancer Institute.
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.
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