Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine if neurosteroids (steroids synthesized in the brain) are produced by enzymes found in steroidogenic tissues, we determined if mRNA for five steroidogenic enzymes could be detected in brain tissues or cultured cells. We detected mRNAs for adrenodoxin, P450scc (cholesterol side-chain cleavage enzyme) and P450c11 beta (11 beta-hydroxylase) but not for P450c17 (17 alpha-hydroxylase/17,20 lyase) or P450c11AS (aldosterone synthase) in rat brains and cultures of rat glial cells. P450scc mRNA abundance in brain or primary glial cultures was approximately 0.01% of that found in the adrenal, but more P450scc mRNA was detected in C6 glial cells. Both P450scc and P450c11 beta mRNAs were most abundant in the cortex, but there were region-specific differences for both mRNAs, and sex-specific differences for P450c11 beta mRNA. P450scc mRNA was equally abundant in mixed glial cultures containing both astrocytes and oligodendrocytes as in astrocyte-enriched cultures, and P450scc immunoreactivity co-localized with GFAP immunoreactivity in cultured astrocytes. P450c11 beta mRNA was not detected in the mixed primary glial cultures for the C6 glioma cell line that synthesize P450scc mRNA, suggesting that glial cells do not synthesize P450c11 beta mRNA. Thus some of the same enzymes involved in steroidogenesis in classic endocrine tissues are found in a cell-specific and region-specific fashion in the brain. Neurosteroids may be derivatives of known classic steroids, and/or may function through non-classic steroid hormone receptors, such as GABAA, N-methyl-D-aspartate, and corticosterone receptors.
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PMID:Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain. 811 31

Regulation of steroidogenesis in classic endocrine tissues is mediated by transcriptional regulation of the P450scc gene, which encodes the first and rate-limiting cholesterol side-chain cleavage enzyme. We previously showed that P450scc messenger RNA is regionally expressed in the adult rat brain, primary glial cultures, and C6 glioma cells. Expression of P450scc in the brain results in the de novo synthesis of neurosteroids, a class of steroid hormones that are active at gamma-aminobutyric acidA and N-methyl-D-aspartate receptors. We determined whether P450scc expression is transcriptionally regulated in neural cells, using the same DNA sequences and nuclear proteins as classic steroidogenic adrenal and Leydig cells. The transcriptional activity of deletional mutants of 2.5 kilobases of the 5'-flanking regulatory region of the rat P450scc gene cloned into a luciferase reporter gene was assessed in mouse adrenocortical Y-1, mouse Leydig MA-10, rat C6 glioma, rat GC somatotrope, and mouse GT1-7 neurosecretory cell lines. P450scc was transcriptionally regulated in Y-1, MA-10, and C6 glioma cells, but not in GC or GT1-7 cells. In one region (-94/-35), putative steroidogenic factor-1-binding sites appeared to be critical for the basal transcriptional activity and cAMP responsiveness in steroidogenic Y-1 and MA-10 cells, but had no function in rat C6 cells. DNA sequences between -94/-130 mediated both basal and cAMP-inducible transcriptional activity in C6 cells. Gel mobility shift assays showed that one nuclear protein binding to DNA sequences between -54 and -35 was abundant in MA-10 and Y-1 cells, but was absent from C6 cells, whereas another nuclear protein, binding to DNA sequences between -94 and -130 was abundant in C6 cells, but was rare in MA-10 cells and absent from Y-1 and other adrenocortical cells. Although the DNA sequence between -94 and -130 contains an Sp1 site, Sp1 did not bind to this site. Nevertheless, this GC-rich region was critical for nuclear protein binding and for basal and cAMP-induced transcriptional regulation in both C6 and MA-10 cells. These observations demonstrate that the rat P450scc gene is transcriptionally regulated in glioma cells, but its regulation in glial cells involves a DNA element different from those used in classic steroidogenic tissues. The results further suggest that steroidogenic factor-1 is not involved in regulating neurosteroidogenesis.
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PMID:Transcriptional regulation of P450scc gene expression in neural and steroidogenic cells: implications for regulation of neurosteroidogenesis. 858 34