To function efficiently, the prefrontal cortex requires signaling by neurotransmitters such as dopamine and norepinephrine. COMT helps maintain appropriate levels of these neurotransmitters in this part of the brain.
COMT has also been demonstrated to play a role in estrogen metabolism through inactivation of the catecholestrogens. Catecholestrogens are formed during the metabolism of estrogens such as estradiol. Catecholestrogen inactivation decreases the cancer-causing potential of these metabolites, while simultaneously increasing the amount of 2-methoxyestradiol, a metabolite that has been shown to inhibit the growth of breast cancer cells. Additionally, COMT polymorphisms have been shown to influence estradiol levels. As Met/Met allele carriers exhibit a 2-3 fold decrease in their ability to degrade catecholestrogens, this results in higher estradiol levels than Val/Val allele carriers. Estradiol clearance is also diminished in both the Met/Met and Met/Val genotypes as opposed to Val/Val genotypes, however there is no significant difference in estrone levels.
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