The beneficial effects of estrogen on liver metabolism explained in breakthrough Science paper from the Royal College of Surgeons in Ireland  and University of California

The female hormone estrogen tends to protect women against high cholesterol and heart disease during the child-bearing years.  This may help explain why premenopausal women are usually protected from developing heart disease and cirrhosis. The molecular mechanism for the beneficial effect of estrogen on liver metabolism  was unknown until a joint study between RCSI and the University of California at Irvine published last month in the Science Journal, Science Signaling, revealed the type of estrogen receptor, the targeted genes and the cellular processes involved in this metabolic response in the liver. The research team led by Dr Ellis Levin at UC Irvine and Prof Brian Harvey at RCSI showed that estrogen binds to a new type of estrogen receptor at the cell membrane (membrane ER) to activate a network of enzymes which inhibit a regulator  (SREB) of genes that drive the synthesis of cholesterol .  The researchers also found that estrogen suppresses lipid synthesis including harmful triglycerides.   The team at RCSI included father and son, Brian and Harry Harvey, and post-doctoral fellow Fiona O’Mahony who identified the estrogen-responsive genes. The UC Irvine team developed a transgenic mouse which expressed only the membrane estrogen receptor which allowed its role in liver metabolism to be understood at the patho-physiological level.  From  these experiments, the two teams were able to provide important insights about how estrogen and membrane ER signalling may suppress the expression of some genes and produce beneficial changes in liver metabolism. The researchers concluded  that their results provide the impetus to develop and test new forms of  pharmacological agonists that only engage the membrane ER and avoid the cancer-producing side-effects of estrogen in the nucleus, and which could contribute to favourable lipid homeostasis, including preventing excessive harmful cholesterol and triglyceride content in the blood that can progress to heart disease and cirrhosis.

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