New research conducted by Northwestern University's Serdar Bulun suggests that endometriosis may be caused by epigenetic defects triggered when an embryo is exposed to environmental toxins. Bulun has spent the past 15 years investigating the disease and he describes his lab's latest findings in the New England Journal of Medicine.
One of the abnormalities he discovered in endometriosis sufferers is the presence of the enzyme aromatase (which produces estrogen) in endometrium, the diseased tissue that exists on pelvic organs and mimics the uterine lining. Normal endometrium, located in the uterine cavity, does not contain aromatase. As a result, women with endometriosis have excessive estrogen in this abnormal tissue found on surfaces of pelvic organs such as the ovaries.
Significantly, Bulun found the protein SF1 that produces aromatase, which is supposed to be shut down, is active in endometriosis. "Estrogen is like fuel for fire in endometriosis," Bulun said. "It triggers the endometriosis and makes it grow fast."
As a result of the aromatase finding, Bulun launched clinical trials in 2004 and 2005 testing aromatase inhibitors - currently used in breast cancer treatment - for women with endometriosis. The drug blocks estrogen formation and secondarily improves progesterone responsiveness. "We came up with a new treatment of choice for post-menopausal women with endometriosis," Bulun explained.
Another molecular abnormality Bulun found is that women with endometriosis have a progesterone receptor that is inappropriately turned off. Normal progesterone action would be beneficial because it blocks the growth of endometriosis. In the absence of appropriate progesterone action, endometriosis tissue remains inflamed and continues to grow. Bulun believes that these abnormalities result from epigenetic defects that occur very early on during embryonic development and may be the result of early exposure to environmental toxins. In fact, other investigators have implicated the environmental pollutant dioxin and the synthetic estrogen DES in the make-up of endometriosis.
"This may be a disease that women are born with," Bulun speculates. "Perhaps when a baby girl is born, it has already been determined that she is predisposed to have endometriosis. Maybe research can now be directed toward the fetal origins of the disease and raise the awareness of how the disease develops."
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Source: Northwestern University