Colin Saldanha, a biology professor at American University, has always been intrigued by the hormone estrogen. Specifically, how the hormone that does so much (for example, it promotes sexual behavior in women but can also increase susceptibility to seizures) does not cause major cross circuit meltdowns. “In the extreme case, once every 28 days, women should be having seizures — and when they do, it’s a condition called Catamenial Epilepsy — but that’s obviously not the norm and there’s the mystery,” Saldanha said. “Somehow, the vertebrate body has figured out a way to produce and provide estrogen to precisely the right part of the body at precisely the right time.” To attempt to find out how the bodies of animals and humans can do this, Saldanha has been studying the brains of songbirds — specifically, adult male zebra finches. Why adult male zebra finches? Male zebra finches sing, but the females do not. During the spring — mating season, when males court prospective mates with their songs — parts of the male birds’ brains nearly double in size only to shrink back to normal size in the fall when mating season has ended. Estrogen is behind the phenomenon.
Previous research on hormone synthesis outlines three ways the body makes and delivers estrogen to different parts: Endocrine signaling (estrogen produced in the ovaries and made available to the entire body through the bloodstream); paracrine signaling (estrogen made in the brain but stays local/ in the area where it was made); autocrine signaling (estrogen made in an individual cell for use in that cell). Recently, Saldanha and colleagues from the University of Massachussetts — Amherst and the University of California — Los Angeles, published research that introduced a fourth and new method of estrogen synthesis to the scientific community: synaptocrine signaling, or at the synapse. Synapses are junctions in the brain across which neurons (cells traditionally viewed as the most important in the central nervous system) use electrical or chemical signals to communicate with another cell downstream. Saldanha and his colleagues originally discovered synaptocrine estrogen synthesis and signaling in 2005. They used a special protein they developed that detects aromatase, a complex enzyme key to estrogen synthesis, and an electron microscope to figure out which specific cells of the songbirds’ brains were capable of making estrogen.
When they saw the protein marking the synapses, they were surprised. “This was startling. There wasn’t even a name for this in the literature. We had to come up with one to describe it. We called it synaptocrine signaling,” said Saldanha, whose research into the synaptic localization of aromatase and estrogen synthesis has been funded since 2002 by more than $3 million in grants from the National Institutes of Health. Synaptocrine signaling is a highly specific form of neuro and hormonal communication. A specific target (a particular neuron) can create and feed high levels of estrogen to another, specific neuron with which it needs to communicate — and here is the key part — to the exclusion of other neighboring cells around the “target” neuron. To make sure their findings were valid, Saldanha and his colleagues did the experiment again and even had someone else conduct it. When all of the experiments ended with the same results, Saldanha and his colleagues submitted their paper to Endocrine Reviews, the Endocrine Society’s research journal, where it was published. Through earlier research, Saldanha uncovered yet another way songbird brains can synthesize estrogen and it presents important implications for research into degenerative brain diseases and conditions in humans such as Alzheimer’s and Parkinson’s diseases, and strokes.
February 7, 2012
Original web page at Science Daily