Human catechol-O-methyltransferase: downregulation by estradiol

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Human catechol-O-methyltransferase: downregulation by estradiol. / Jiang, H; Xie, T; Ramsden, David; Ho, SL.

In: Neuropharmacology, Vol. 45(7), 01.12.2003, p. 1011-1018.

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Jiang, H, Xie, T, Ramsden, D & Ho, SL 2003, 'Human catechol-O-methyltransferase: downregulation by estradiol', Neuropharmacology, vol. 45(7), pp. 1011-1018.

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Jiang, H ; Xie, T ; Ramsden, David ; Ho, SL. / Human catechol-O-methyltransferase: downregulation by estradiol. In: Neuropharmacology. 2003 ; Vol. 45(7). pp. 1011-1018.

Bibtex

@article{f7e0a32a384c4617ba4f05422339ec37,
title = "Human catechol-O-methyltransferase: downregulation by estradiol",
abstract = "Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Previously we reported that physiological concentrations of 17beta-estradiol (E2) down-regulated steady-state 1.3-kb COMT mRNA levels in MCF-7 cells. In this study, we investigated whether similar reductions occurred in a glial cell line (U138MG) and whether COMT protein and activity levels paralleled the reduction in COMT mRNA levels in MCF-7 cells. In addition, we explored the mechanism of E2 action. E2 had no effect on COMT mRNA levels in U138MG cells, but significantly reduced COMT protein and activity in MCF-7 cells (activity by 53% at 10(-7) M of E2, by 45% at 10(-8) M, and by 28% at 10(-9) M relative to non-E2-treated cells). A specific estrogen receptor antagonist (ICI 182780) blocked these estrogenic effects. Estrogen receptor in nuclear extracts of MCF-7 cells, which were pretreated with E2 (10(-9) M) for 48 h, bound to the whole proximal and distal promoter regions, as determined by electrophoretic mobility shift analysis (EMSA). We propose that E2 decreased COMT activity through down-regulation of its gene and protein expression mediated via ER interaction with response elements in the promoter region of the gene. Our findings may explain the lower of COMT activity in women compared to that in men, and, in part, the beneficial effects of E2 therapy in post-menopausal Parkinson's disease patients. (C) 2003 Elsevier Ltd. All rights reserved.",
keywords = "dopamine, S-adenosyl-L-methionine, 17 beta-estradiol, estrogen response element, Parkinson's disease, catechol-O-methyltransferase, estrogen receptor",
author = "H Jiang and T Xie and David Ramsden and SL Ho",
year = "2003",
month = dec,
day = "1",
language = "English",
volume = "45(7)",
pages = "1011--1018",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Human catechol-O-methyltransferase: downregulation by estradiol

AU - Jiang, H

AU - Xie, T

AU - Ramsden, David

AU - Ho, SL

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Previously we reported that physiological concentrations of 17beta-estradiol (E2) down-regulated steady-state 1.3-kb COMT mRNA levels in MCF-7 cells. In this study, we investigated whether similar reductions occurred in a glial cell line (U138MG) and whether COMT protein and activity levels paralleled the reduction in COMT mRNA levels in MCF-7 cells. In addition, we explored the mechanism of E2 action. E2 had no effect on COMT mRNA levels in U138MG cells, but significantly reduced COMT protein and activity in MCF-7 cells (activity by 53% at 10(-7) M of E2, by 45% at 10(-8) M, and by 28% at 10(-9) M relative to non-E2-treated cells). A specific estrogen receptor antagonist (ICI 182780) blocked these estrogenic effects. Estrogen receptor in nuclear extracts of MCF-7 cells, which were pretreated with E2 (10(-9) M) for 48 h, bound to the whole proximal and distal promoter regions, as determined by electrophoretic mobility shift analysis (EMSA). We propose that E2 decreased COMT activity through down-regulation of its gene and protein expression mediated via ER interaction with response elements in the promoter region of the gene. Our findings may explain the lower of COMT activity in women compared to that in men, and, in part, the beneficial effects of E2 therapy in post-menopausal Parkinson's disease patients. (C) 2003 Elsevier Ltd. All rights reserved.

AB - Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Previously we reported that physiological concentrations of 17beta-estradiol (E2) down-regulated steady-state 1.3-kb COMT mRNA levels in MCF-7 cells. In this study, we investigated whether similar reductions occurred in a glial cell line (U138MG) and whether COMT protein and activity levels paralleled the reduction in COMT mRNA levels in MCF-7 cells. In addition, we explored the mechanism of E2 action. E2 had no effect on COMT mRNA levels in U138MG cells, but significantly reduced COMT protein and activity in MCF-7 cells (activity by 53% at 10(-7) M of E2, by 45% at 10(-8) M, and by 28% at 10(-9) M relative to non-E2-treated cells). A specific estrogen receptor antagonist (ICI 182780) blocked these estrogenic effects. Estrogen receptor in nuclear extracts of MCF-7 cells, which were pretreated with E2 (10(-9) M) for 48 h, bound to the whole proximal and distal promoter regions, as determined by electrophoretic mobility shift analysis (EMSA). We propose that E2 decreased COMT activity through down-regulation of its gene and protein expression mediated via ER interaction with response elements in the promoter region of the gene. Our findings may explain the lower of COMT activity in women compared to that in men, and, in part, the beneficial effects of E2 therapy in post-menopausal Parkinson's disease patients. (C) 2003 Elsevier Ltd. All rights reserved.

KW - dopamine

KW - S-adenosyl-L-methionine

KW - 17 beta-estradiol

KW - estrogen response element

KW - Parkinson's disease

KW - catechol-O-methyltransferase

KW - estrogen receptor

M3 - Article

C2 - 14573393

VL - 45(7)

SP - 1011

EP - 1018

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -