The location of the Syt IV protein, known for regulating hormones critical to women's health, had long baffled scientists. Finally, researchers at the University of Wisconsin-Madison have identified the secret locations as the pituitary gland.
Scientists found that the "rogue protein," whose main location and function were unknown until now, is located in a specific area of the pituitary gland.
The puzzling protein acts as control knob and may adjust the release of the two hormones that come almost exclusively from the posterior pituitary: oxytocin, which controls many reproductive functions, and vasopressin, which controls fluid balance.
"The findings raise very interesting possibilities for women's health, in which rising and falling hormone levels play a key role in many biological processes," Nature magazine quoted senior author Meyer Jackson, a professor of physiology at the UW-Madison School of Medicine and Public Health (SMPH), as saying.
The research focused on Syt IV, which is a member of the synaptotagmin family of 17 proteins, present in both mice and humans.
Synaptotagmins are usually embedded in the membranes of small sacs, or vesicles, filled with neurotransmitters and hormones within nerve terminals.
At the time when an electrical impulse from one cell reaches a nerve terminal, Syt IV triggers the release of calcium.
Calcium, in its turn triggers the spilling out of the vesicle's contents - neurotransmitters and hormones - so they can act on other cells.
"Most synaptotagmins are triggering molecules that drive a vesicle's membrane into the membrane that surrounds a neighboring cell so that chemicals inside the vesicle can come out," said Jackson.
However, Syt IV is different as it doesn't bind to calcium and is found only sparsely in most parts of the brain.
But the researchers were shocked a few years ago after they discovered large amounts of it in the posterior pituitary, one of the three primary parts of the gland.
For the study, the researchers conducted high-powered biophysical measurements, and then compared the pituitaries from normal mice and mice in which Syt IV had been knocked out.
It was found that like other members of the synaptotagmin family, Syt IV resides on vesicles. But unlike the others, Syt IV doesn't trigger neurotransmitter or hormone release.
"It does not simply translate a calcium signal into a command for hormone release. Unlike other synaptotagmins, Syt IV tunes the triggering command and determines whether the same electrical impulse will let a large or small amount of hormone out of the nerve terminal," said Jackson.
This ability to modulate hormone release may have important implications for pregnancy, birth, lactation and the menstrual cycle, all of which are linked to fluctuations in oxytocin levels.
"Any change in the body that entails releasing more or less of this hormone into the bloodstream could well be a result of the brain's making more or less of this protein," said Jackson.
He further added that more studies will be needed to better understand the protein.
The study appeared in the recent issue of Nature Neuroscience.