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Steroid 21-hydroxylase expression in cultured rat astrocytes
journal contribution
posted on 2003-10-01, 00:00 authored by M Lovelace, Thomas Watson, Garth StephensonGarth StephensonOver the past decade or so it has become widely recognised that the brain is a significant steroidogenic organ. Many publications have highlighted the ability of the brain to synthesise and interconvert a large number of steroid products including cholesterol, progesterone and testosterone. In this study, in vitro experiments were performed to determine if 21-hydroxylation of steroids is undertaken by rat brain astrocytes in culture. This is a common reaction that occurs in the adrenal gland and other organs in mammals, catalysing the conversion of pregn-4-ene-3,20-dione (progesterone) to 21-hydroxypregn-4-ene-3,20-dione (deoxycorticosterone).
Previous reports have indicated that 21-hydroxylation occurs within the rat brain, however, the precise identity of the cells expressing 21-hydroxylase has not yet been determined. Several metabolites, such as 5α-pregnan-3α-ol-20-one (tetrahydroprogesterone) and 3α,21-dihydroxy-5-pregnan-20-one (tetrahydrodeoxycorticosterone) were of particular interest because of their modulatory role in neuronal function, such as their agonist activity at γ-aminobutyric acid (GABAA) receptors.
Evidence was obtained for the expression of peripheral 21-hydroxylase enzyme (P450c21) in cultured rat brain astrocytes by a combination of mass spectroscopy and molecular biology techniques. This is a significant finding as expression of 21-hydroxylase within astrocytes may be indicative of a wider role for these cells in modulating neuronal behaviour.
Previous reports have indicated that 21-hydroxylation occurs within the rat brain, however, the precise identity of the cells expressing 21-hydroxylase has not yet been determined. Several metabolites, such as 5α-pregnan-3α-ol-20-one (tetrahydroprogesterone) and 3α,21-dihydroxy-5-pregnan-20-one (tetrahydrodeoxycorticosterone) were of particular interest because of their modulatory role in neuronal function, such as their agonist activity at γ-aminobutyric acid (GABAA) receptors.
Evidence was obtained for the expression of peripheral 21-hydroxylase enzyme (P450c21) in cultured rat brain astrocytes by a combination of mass spectroscopy and molecular biology techniques. This is a significant finding as expression of 21-hydroxylase within astrocytes may be indicative of a wider role for these cells in modulating neuronal behaviour.
History
Journal
Brain research bulletinVolume
61Issue
6Pagination
609 - 615Publisher
Elsevier ScienceLocation
New York, N.Y.Publisher DOI
ISSN
0361-9230eISSN
1873-2747Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2003, Elsevier IncUsage metrics
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No categories selectedKeywords
L - Leucine methyl estermicrogliaP450c21tetrahydrodeoxycorticosteronetetrahydroprogesteroneScience & TechnologyLife Sciences & BiomedicineNeurosciencesNeurosciences & NeurologyL-leucine methyl esterCYTOKINE-MEDIATED REGULATIONL-ASCORBIC-ACIDANDROGEN BIOSYNTHESISOVARIAN-FUNCTIONBRAININHIBITIONMETABOLISMCLONINGSYSTEMENZYME
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