Despite the popularity of popping DHEA pills among dietary supplement enthusiasts in search of a fountain of youth, the naturally occurring form of DHEA has never been shown to be anything more than a way station on the biochemical trail leading to production of more exciting compounds, such as the sex hormones, testosterone and estrogen.

But in the most recent tissue of the Proceedings of the National Academy of Sciences, UCSF researchers report that in the brains of mice -- and very likely in the brains of humans as well -- DHEA and a related, sulfur-containing version of the compound, called DHEAS, can stimulate the growth of nerve cell fibers needed to form electrical connections in the brain.

In the mouse embryo, enzymes that are needed to make DHEA and DHEAS in the brain are located at brain sites where nerve cells extend branches to connect the thalamus to more highly evolved regions in the brain's cortex, the UCSF researchers have determined.

Nerve cells from the cortex maintained in laboratory cultures are stimulated differently by DHEA -- short for dyhydroepiandrosterone -- and by DHEAS, according to Synthia H. Mellon, associate professor of obstetrics, gynecology and reproductive sciences at UCSF, and assistant research scientist Nathalie A. Compagnone, PhD.

DHEA fosters the growth of fibers that transmit signals to other nerve cells, while DHEAS stimulates growth of fibers that receive signals from other nerve cells, the UCSF researchers discovered. These growth-stimulating properties appear in cells that undergo rapid biochemical changes in response to DHEA and DHEAS.

"These studies provide evidence that DHEA and DHEAS exert biological actions and are not simply sex hormone precursors," Mellon says. "The regulated production of DHEA and DHEAS in the embryonic brain may play a crucial role in organizing neural connections."

"DHEA and DHEAS do not appear to be slow-acting hormones that attach to specific receptors on cells like classic hormones. Instead they cause rapid changes in nerve cells, like neurotransmitters do."

DHEA has primarily been thought of as a compound made by the adrenal glands, which sit atop the kidneys. The adrenal gland's production of DHEA, which is converted into sex hormones, peaks at about age 20, at higher levels in men than women. Thereafter, blood concentrations of DHEA decline steadily throughout adulthood in both sexes, typically dropping to 15 to 20 percent of youthful levels in old age. This decline has led researchers to search for an association among blood levels of DHEA, signs of aging, and diseases associated with aging.

In animal studies that may be relevant to investigations of memory impairment in Alzheimer's, old mice -- which normally perform poorly in learning tests with mazes -- were able to learn as well as young mice when given DHEA with their drinking water, according to Owen Wolkowitz, MD, a professor of psychiatry at UCSF.

Wolkowitz and UCSF colleague Louann Brizendine, MD, associate clinical professor of psychiatry, are now conducting clinical trials to investigate any potential benefits of DHEA in Alzheimer's patients and in individuals who are clinically depressed. In a preliminary study, Wolkowitz found that depressed DHEA recipients reported improved psychological well-being and mood, and that they had better recall in tests of memory.

The new research findings by Compagnone and Mellon raise many questions about the role of DHEA and the related sulfur-containing compound, DHEAS, in normal brain development, in the maintenance of brain function in adulthood and in neurodegenerative diseases such as Alzheimer's.

It also is not clear if DHEA and DHEAS made by the human adrenal gland act on the brain, or whether the brain continues to make its own supply of these steroids after the framework for the brain's neural architecture is completed about a year after birth, Mellon says.

By Jeffrey Norris

1st appeared 4/27/98

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