See What HealthDay Can Do For You
Contact Us

Estrogen Metabolism May Have an Impact on Stroke Recovery

2-methoxyestradiol inhibits proliferation, pro-inflammatory responses, phagocytosis in microglia

brain skull

MONDAY, Jan. 25, 2016 (HealthDay News) -- 2-methoxyestradiol (2-ME), an endogenous metabolite of estradiol, inhibits proliferation, pro-inflammatory responses, and phagocytosis in microglia, according to a study published online Jan. 5 in the American Journal of Physiology-Endocrinology and Metabolism.

Sara A. Schaufelberger, from the University Hospital Zurich, and colleagues compared the effects of estradiol, 2-hydroxyestradiol (2-OE; estradiol metabolite produced by cytochrome P450 [CYP450]), and 2-ME (formed by catechol-O-methyltransferase [COMT] acting on 2-OE) on microglial DNA synthesis, cell proliferation, activation, and phagocytosis.

The researchers found that for inhibition of microglia DNA synthesis, 2-ME and 2-OE were about three- and 10-fold more potent that estradiol, respectively. Pharmacological inhibitors of CYP450 and COMT reduced the anti-mitogenic effects of estradiol. COMT inhibition blocked 2-OE to 2-ME conversion and the anti-mitogenic effects of 2-OE but not 2-ME. Microglia expressed estrogen receptor (ER)-β and GPR30, but did not express ER-α. Microglial proliferation was inhibited by an ER-β agonist, but not by an ER-α agonist or G1 (GPR30 agonist). An ERα/β antagonist (ICI182780) partially reversed the anti-proliferative effects of estradiol, but not 2-OE or 2-ME, while an ER-α antagonist or G15 (GPR30 antagonist) did not. 2-ME inhibited the effect of lipopolysaccharide, which increased microglia inducible nitric oxide synthase and cyclooxygenase-2 expression and the phagocytosing activity of microglia.

"2-ME could be of potential therapeutic use in post-ischemic stroke injuries," the authors write. "Inter-individual differences in estradiol metabolism might affect the individual's ability to recover from stroke."

Full Text

Physician's Briefing


HealthDay is the world’s largest syndicator of health news and content, and providers of custom health/medical content.

Consumer Health News

A health news feed, reviewing the latest and most topical health stories.

Professional News

A news feed for Health Care Professionals (HCPs), reviewing latest medical research and approvals.