April 2, 2012
Estrogen Is Responsible For Slow Wound Healing In Women
New research in the FASEB Journal suggests that a lipid pathway (15-lipoxygenase-Lipoxin A4) is less active in females because estrogen reduces the activity and expression of this pathway
Estrogen causes wounds in women to heal slower than in men - who have lower levels of estrogen - says a new study published in the April 2012 issue of the FASEB Journal. In the report, scientists from the University of California, Berkeley, provide the first evidence that mild injury response in the eye is fundamentally different in males and females because of estrogen. This discovery provides new clues for successfully treating a wide range of inflammatory diseases such as dry eye disease, rheumatoid arthritis, lupus, multiple sclerosis, and scleroderma.
To make this discovery, Gronert and colleagues administered a mild abrasion injury to the front of the eye of genetically similar male and female mice, and analyzed wound healing by image analysis. To test the role of estrogen, they gave male mice estrogen eye drops and/or drugs that activate specific estrogen receptors. Gene expression of essential enzymes was quantified for the formation of protective lipid signals, specific receptors that mediate their bioactivity, as well as estrogen receptors in mouse corneas and human/mouse epithelial cell cultures. The formation of protective lipid signals was analyzed by a mass-spectrometry based lipidomic method. They found that estrogen negatively affects a highly evolved protective lipid circuit, called "15-lipoxygenase-Lipoxin A4" that has recently emerged as an important protective pathway in many diseases. This pathway balances the activity of pro-inflammatory signals to promote wound healing and to keep inflammation within safe ranges.
"This study goes a long way to explaining gender differences in inflammation and its resolution," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "It's long been known that women suffer more than men from chronic inflammatory diseases such as lupus or rheumatoid arthritis; this study suggests that estrogen itself is responsible for that difference and pinpoints the molecular pathways that estrogen affects. Molecules that promote the resolution of inflammation show promise as new treatments for autoimmune disease."
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