StAR appears to do its best work when it takes the shape of a molten globule. That is not news from astronomers or cosmologists, but from the molecular biology lab of Walter L. Miller, MD, professor of pediatric endocrinology at UC San Francisco. Miller's group is working to find out how cells make steroid hormones, chemicals that are essential for life, for health and for reproduction because they control the body's salt balance, sugar balance and sexual function. StAR - steroidogenic acute regulatory protein -- is an unusual protein that recently has been shown to perform a key role in the steroid-making system. In a paper in the June 22, 1999 issue of the journal Proceedings of the National Academy of Sciences, Miller, UCSF postdoctoral fellow Himangshu Bose and their colleagues report that the StAR protein partially unfolds from its finished shape in order to take a shape that allows it to work inside the cell. In protein-folding jargon, a partially unfolded protein is called a "molten globule."
Cells in the adrenal and sex glands manufacture steroid hormones by changing cholesterol into related chemicals, in a process that involves many steps. For the first step, cholesterol has to be transported into mitochondria, small energy-generating spheres inside the cell. In work published over the past few years, Miller's group and their colleagues from other universities have demonstrated that StAR helps speed up this cholesterol-transfer process. These groups also have cloned the gene that controls the StAR protein, and have shown that a rare inherited disease is caused by mutations of that gene. The disease provides stark proof of the essential role of steroid hormones.
Children born with the rare disease, congenital lipoid adrenal hyperplasia
(lipoid CAH) cannot make steroid hormones in part because they lack a
functioning StAR protein. "Many of these children die in infancy for lack of
mineralcorticoids, the hormones that regulate salt balance in t
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Contact: Janet Basu
jbasu@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
22-Jun-1999