THE CATECHOL ESTROGEN, 2‐HYDROXYESTRADIOL, INHIBITS CATECHOL‐O‐METHYLTRANSFERASE ACTIVITY IN NEUROBLASTOMA CELLS

Tom Lloyd, Judith Weisz, Xandra O. Breakefield

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Abstract— The hydroxylation of estrone and estradiol at C2 to their respective catechol estrogens has been demonstrated by others with in vitro preparations from rat hypothalamic tissue. The subsequent methylation of these catechol estrogens by catechol‐O‐methyltransferase (COMT) in rat brain extracts has also been observed. Therefore, in specific sites in brain, 2‐hydroxylation of estrogens could play a significant role in the regulation of catecholamine metabolism. To evaluate the potential physiological significance of these interactions, we studied cultured murine neuroblastoma cells where the effect of 2‐hydroxyestradiol on COMT activity could be investigated in living cells and in cell homogenates. The addition of 2‐hydroxyestradiol to the cultures caused a specific dose‐dependent reduction in the formation of methylated products from the catecholamine, dopamine. The properties of COMT activity in the cell homogenates were examined and optimized with respect to the substrate, pH, concentrations of Mg2+, and the co‐factor, S‐adenosylmethionine. The catechol substrate. 3, 4‐dihydroxybenzoic acid, and 2‐hydroxyestradiol were both methylated by the cell homogenates. Inhibitor studies confirmed that both methylations were due to COMT. Furthermore, the catechol estrogen inhibited catechol methylation competitively at micromolar levels. These findings are consistent with the hypothesis that catechol estrogens are endogenous modulators of catecholamine metabolism.

Original languageEnglish (US)
Pages (from-to)245-250
Number of pages6
JournalJournal of neurochemistry
Volume31
Issue number1
DOIs
StatePublished - Jul 1978

Fingerprint

Catechol Estrogens
Neuroblastoma
Methylation
Catecholamines
Metabolism
Rats
Brain
Hydroxylation
Estrone
Substrates
Modulators
Estradiol
Dopamine
Estrogens
Cells
Tissue
Acids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

@article{d9b9f27ebb964d34a3cb4af11c4d8b89,
title = "THE CATECHOL ESTROGEN, 2‐HYDROXYESTRADIOL, INHIBITS CATECHOL‐O‐METHYLTRANSFERASE ACTIVITY IN NEUROBLASTOMA CELLS",
abstract = "Abstract— The hydroxylation of estrone and estradiol at C2 to their respective catechol estrogens has been demonstrated by others with in vitro preparations from rat hypothalamic tissue. The subsequent methylation of these catechol estrogens by catechol‐O‐methyltransferase (COMT) in rat brain extracts has also been observed. Therefore, in specific sites in brain, 2‐hydroxylation of estrogens could play a significant role in the regulation of catecholamine metabolism. To evaluate the potential physiological significance of these interactions, we studied cultured murine neuroblastoma cells where the effect of 2‐hydroxyestradiol on COMT activity could be investigated in living cells and in cell homogenates. The addition of 2‐hydroxyestradiol to the cultures caused a specific dose‐dependent reduction in the formation of methylated products from the catecholamine, dopamine. The properties of COMT activity in the cell homogenates were examined and optimized with respect to the substrate, pH, concentrations of Mg2+, and the co‐factor, S‐adenosylmethionine. The catechol substrate. 3, 4‐dihydroxybenzoic acid, and 2‐hydroxyestradiol were both methylated by the cell homogenates. Inhibitor studies confirmed that both methylations were due to COMT. Furthermore, the catechol estrogen inhibited catechol methylation competitively at micromolar levels. These findings are consistent with the hypothesis that catechol estrogens are endogenous modulators of catecholamine metabolism.",
author = "Tom Lloyd and Judith Weisz and Breakefield, {Xandra O.}",
year = "1978",
month = "7",
doi = "10.1111/j.1471-4159.1978.tb12455.x",
language = "English (US)",
volume = "31",
pages = "245--250",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

THE CATECHOL ESTROGEN, 2‐HYDROXYESTRADIOL, INHIBITS CATECHOL‐O‐METHYLTRANSFERASE ACTIVITY IN NEUROBLASTOMA CELLS. / Lloyd, Tom; Weisz, Judith; Breakefield, Xandra O.

In: Journal of neurochemistry, Vol. 31, No. 1, 07.1978, p. 245-250.

Research output: Contribution to journalArticle

TY - JOUR

T1 - THE CATECHOL ESTROGEN, 2‐HYDROXYESTRADIOL, INHIBITS CATECHOL‐O‐METHYLTRANSFERASE ACTIVITY IN NEUROBLASTOMA CELLS

AU - Lloyd, Tom

AU - Weisz, Judith

AU - Breakefield, Xandra O.

PY - 1978/7

Y1 - 1978/7

N2 - Abstract— The hydroxylation of estrone and estradiol at C2 to their respective catechol estrogens has been demonstrated by others with in vitro preparations from rat hypothalamic tissue. The subsequent methylation of these catechol estrogens by catechol‐O‐methyltransferase (COMT) in rat brain extracts has also been observed. Therefore, in specific sites in brain, 2‐hydroxylation of estrogens could play a significant role in the regulation of catecholamine metabolism. To evaluate the potential physiological significance of these interactions, we studied cultured murine neuroblastoma cells where the effect of 2‐hydroxyestradiol on COMT activity could be investigated in living cells and in cell homogenates. The addition of 2‐hydroxyestradiol to the cultures caused a specific dose‐dependent reduction in the formation of methylated products from the catecholamine, dopamine. The properties of COMT activity in the cell homogenates were examined and optimized with respect to the substrate, pH, concentrations of Mg2+, and the co‐factor, S‐adenosylmethionine. The catechol substrate. 3, 4‐dihydroxybenzoic acid, and 2‐hydroxyestradiol were both methylated by the cell homogenates. Inhibitor studies confirmed that both methylations were due to COMT. Furthermore, the catechol estrogen inhibited catechol methylation competitively at micromolar levels. These findings are consistent with the hypothesis that catechol estrogens are endogenous modulators of catecholamine metabolism.

AB - Abstract— The hydroxylation of estrone and estradiol at C2 to their respective catechol estrogens has been demonstrated by others with in vitro preparations from rat hypothalamic tissue. The subsequent methylation of these catechol estrogens by catechol‐O‐methyltransferase (COMT) in rat brain extracts has also been observed. Therefore, in specific sites in brain, 2‐hydroxylation of estrogens could play a significant role in the regulation of catecholamine metabolism. To evaluate the potential physiological significance of these interactions, we studied cultured murine neuroblastoma cells where the effect of 2‐hydroxyestradiol on COMT activity could be investigated in living cells and in cell homogenates. The addition of 2‐hydroxyestradiol to the cultures caused a specific dose‐dependent reduction in the formation of methylated products from the catecholamine, dopamine. The properties of COMT activity in the cell homogenates were examined and optimized with respect to the substrate, pH, concentrations of Mg2+, and the co‐factor, S‐adenosylmethionine. The catechol substrate. 3, 4‐dihydroxybenzoic acid, and 2‐hydroxyestradiol were both methylated by the cell homogenates. Inhibitor studies confirmed that both methylations were due to COMT. Furthermore, the catechol estrogen inhibited catechol methylation competitively at micromolar levels. These findings are consistent with the hypothesis that catechol estrogens are endogenous modulators of catecholamine metabolism.

UR - http://www.scopus.com/inward/record.url?scp=0018143592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018143592&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.1978.tb12455.x

DO - 10.1111/j.1471-4159.1978.tb12455.x

M3 - Article

C2 - 671023

AN - SCOPUS:0018143592

VL - 31

SP - 245

EP - 250

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -