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The Steroidogenic Acute Regulatory Protein Is Expressed in Steroidogenic Cells of the Day-Old Brain

Scott Department of Urology (S.R.K., D.J.L.), Huffington Center on Aging (R.G.S.), Molecular and Cellular Biology (R.G.S., D.J.L.), Baylor College of Medicine, Houston, Texas 77030; Center for Dementia Research, Nathan Kline Institute, and Departments of Psychiatry, Physiology & Neuroscience, New York University School of Medicine (S.D.G.), Orangeburg, New York 10962; and Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center (T.I., K.L.P.), Dallas, Texas 75390

Address all correspondence and requests for reprints to: Dr. Steven R. King, Room N730, Scott Department of Urology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3498. E-mail: srking{at}bcm.tmc.edu.

Although recent research has focused on the fundamental role(s) of steroids synthesized de novo in the brain on development, the mechanism by which production of these neurosteroids is regulated remains unclear. Steroid production in peripheral tissues is acutely regulated by the steroidogenic acute regulatory (StAR) protein, which mediates the rate-limiting step in steroid biosynthesis: the intramitochondrial delivery of cholesterol to cytochrome P450scc for conversion to steroid. We recently demonstrated that StAR is present in discrete cell types in the adult brain, suggesting that neurosteroid production is mediated by StAR. Nevertheless, little is known regarding the presence of StAR in the developing brain. In the present study, the presence of StAR and for the first time, its homolog, the putative cholesterol transport protein metastatic lymph node 64 (MLN64), were defined in the neonatal mouse brain using immunocytochemical techniques. Both StAR and MLN64 were found to be present in the brain with staining patterns characteristic to each protein, indicating the authenticity of StAR and MLN64 immunoreactivity. Furthermore, we found MLN64 to be expressed in the adult brain as well, apparently at higher levels than StAR. Importantly, StAR protein is present in cells that also express P450scc. These data suggest that, as with the adult, neurosteroid production during development occurs through a StAR-mediated pathway.

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