Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #213096
Title: ESTROGEN REPLACEMENT THERAPY REDUCES TOTAL PLASMA HOMOCYSTEINE AND CONCURRENTLY ENHANCES GENOMIC DNA METHYLATION IN POSTMENOPAUSAL WOMEN

Author
item FRISO, SIMONETTA - UNIVERSITY OF VERONA
item Lamon-Fava, Stefania
item JANG, HYERAN - TUFTS UNIVERSITY
item Schaefer, Ernst
item CORROCHER, ROBERTO - UNIVERSITY OF VERONA
item Choi, Sang-Woon

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2006
Publication Date: 4/1/2007
Citation: Friso, S., Lamon-Fava, S., Jang, H., Schaefer, E., Corrocher, R., Choi, S. 2007. Estrogen replacement therapy reduces total plasma homocysteine and concurrently enhances genomic dna methylation in postmenopausal women. British Journal of Nutrition. 97(4):617-621.

Interpretive Summary: Although estrogen replacement therapy has been known to have a protective effect of colon cancer, we still do not know the exact mechanism. Recent studies suggest that estrogen replacement therapy reduces the blood concentration of homocysteine, which is an amino acid and reflects the derangement of one-carbon metabolism which regulates DNA metabolism. In this study we enrolled thirteen postmenopausal women and evaluated the effect of estrogen replacement therapy on the blood homocysteine concentration and DNA metabolism. We observed that estrogen replacement therapy reduces the blood homocysteine concentration and enhances DNA methylation, a molecular phenomenon which regulates critical gene expression. This result suggests a mechanism by which estrogen replacement therapy reduces the risk of colon caner.

Technical Abstract: Although estrogen replacement therapy (ERT), which can affect the risk of major cancers, has been known to reduce total plasma homocysteine concentrations in postmenopausal women, the mechanisms and subsequent molecular changes have not yet been defined. To investigate the effect of ERT on homocysteine metabolism thirteen healthy postmenopausal women were enrolled in a placebo-controlled, randomized, cross-over study consisting of two 8-week long different phases, placebo and conjugated equine estrogen (CEE, 0.625 mg/day). Concentrations of total plasma homocysteine, folate, B-6, and B-12 were measured by conventional methods. Genomic DNA methylation was measured by a new LC/MS method and promoter methylation status of the ER', ER', and p16 genes was analyzed by methylation-specific PCR after bisulfite treatment. The CEE phase demonstrated a significantly decreased mean of total plasma homocysteine concentrations compared with the placebo phase [14.17 umol/L (13.28-15.08) vs 18.71 (16.77-20.86), p<0.05] but there was no difference in the blood concentrations of three B vitamins. The CEE phase also showed a significantly increased genomic DNA methylation in peripheral mononuclear cells compared with the placebo phase (2.85+/-0.12 ng methylcytosine/ug DNA vs 2.40+/-0.15, p<0.05). However, there was no difference in promoter methylation in the ER(alpha), ER(beta) and p16 genes. This study demonstrates that decreased homocysteinemia by CEE therapy parallels with increased genomic DNA methylation, suggesting a new candidate mechanism by which ERT affects the risk of cancers and a new candidate biomarker for the estrogen-related carcinogenesis.