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 language||English (US)|
|Number of pages||6|
|Journal||Journal of neurochemistry|
|State||Published - Jul 1978|
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience