Immunocytochemical Localization and Biological Activity of Hydroxysteroid
Sulfotransferase in the Frog Brain |
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Authors: | Delphine Beaujean Ayikoe G Mensah-Nyagan Jean-Luc Do-Rego Van Luu-The Georges Pelletier Hubert Vaudry |
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Institution: | European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U 413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France; MRC Group in Molecular Endocrinology, Laval University Hospital Center, Québec, Canada |
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Abstract: | Abstract : Biosynthesis of the neuroactive steroids pregnenolone sulfate (?5PS) and dehydroepiandrosterone sulfate (DHEAS) is catalyzed by the enzyme hydroxysteroid sulfotransferase (HST), which transfers the sulfonate moiety from 3'-phosphoadenosine 5' -phosphosulfate (PAPS) on thye 3-hydroxy site of steroids. Although high concentrations of ?5PS and DHEAS have been detected in the rat brain, the anatomical localization of HST in the CNS has never been determined. Using an antiserum against rat liver HST, we have investigated the distribution of HST-like Immunoreactivity in the CNS of the frog Rana ridibunda. Two populations of HST-immunoreactive neurons were observed in the hypothalamus, and several bundless of positive nerves fibers were visualized in the telencephalon and diencephalon. lncubation of frog brain homogenates with 35S]PAPS and 3H] pregnenolone yielded the formation of several 3H, 35S-labeled compounds, including ?5PS and testosterone sulfate. When 3] dehydroepiandrosterone and 35S]PAPS were used as precursors, one of the 3H, 35S-labeled metabolities coeluted with DHEAS. Neosynthesis of 3H]?5PS and 3H]DHEAS was reduced significantly by 2,4-dichloro-6-nitrophenol, a specific inhibitor of sulfotransferases. The present study provides the first immunocytochemical mapping of HSt in the brain. Our data also demonstrate for the first time that biopsynthesis of the highly poten neuroactive steroids ?5PS and DHEAS occurs in the CNS of nonmammalian vertebrates. |
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Keywords: | Hydroxy steroid sulfortransferase Pregnenolone sulfate Dehydroepiandrosterone sulfate Neuroactive steroids Immunohistochemical mapping Enzymatic activity |
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