Drs. Brann and Mahesh co-edit journal issue on estrogen action in the brain

August 06, 2008

Estrogen's action in the brain is the focus of a special August issue of Molecular and Cellular Endocrinology co-edited by Dr. Darrell W. Brann, Regents Professor of Neurology and associate director of the Institute of Neuroscience at the Medical College of Georgia.

Dr. Virendra B. Mahesh, chair emeritus of the MCG Department of Physiology and Endocrinology, also is a co-editor of the journal that explores estrogen's work in the brain such as protecting neurons and enabling learning and memory throughout life.

"There is no doubt reproduction is a primary function of estrogen, but estrogen has lots of functions, probably hundreds," says Dr. Brann, a professor in the MCG Schools of Medicine and Graduate Studies.

In the last decade, scientists have learned that neurons and the supportive glia cells in the brain locally produce estrogen via the enzyme aromatase. Estrogen receptors are in the cell nucleus and membrane of men and women, Dr. Brann says. "It's only recently that we've had the tools to better study what their function could be."

His studies shifted from estrogen's impact on reproduction to its potential in helping brain cells survive a stroke. In this issue, Dr. Brann shows how a protein that interacts with estrogen receptors in the brain enables the hormone to act quickly - as it likely would after a stroke - and more slowly as it does in ovulation.

Estrogen classically works by regulating genes, entering a cell nucleus and interacting with the DNA in a process that can take hours, says Dr. Brann. Scientists recently learned of a fast track that enables estrogen to act within minutes. He's found the protein PELP-1 is one way estrogen can do both.

"This is a very unique protein that can be center stage for both actions," he says. He wants to know if estrogen uses this fast track in response to a stroke and suspects that it uses both modes. "It's kind of interesting that you would recruit the brain production of these hormones possibly as a protective mechanism," Dr. Brann says. "It may be that estrogen has been protecting you throughout many years then at menopause, when estrogen levels drop, it cannot help the brain overcome a massive insult such as a stroke. When estrogen falls, maybe this PELP-1 falls too. It's known that stroke risk goes up after menopause as well as the risk for many other neurodegenerative disorders."

Estrogen's impact on the cell's powerhouse, the mitochondria, is the focus of an article by Dr. James W. Simpkins, chair of the Department Pharmacology and Neuroscience and director of the Institute for Aging and Alzheimer's Disease Research at the University of North Texas Health Science Center in Fort Worth. Dr. Simpkins documents estrogen receptors in the mitochondria, showing that one way the hormone may protect neurons is by helping regulate these powerhouses that enable cell survival.

Other articles explore brain estrogen's impact on the dopaminergic cells, the target for Parkinson disease; its role in regulating progesterone; and in communication in the hypothalamus, a portion of the brain involved in movement and mood.
Dr. Brann, a 1990 graduate of the MCG School of Graduate Studies, is a reviewer for Molecular and Cellular Endocrinology.

Medical College of Georgia at Augusta University

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