title: Adipocyte-derived factor as a modulator of oxidative estrogen metabolism: implications for obesity and estrogen-dependent breast cancer.
abstract: The role of body fat as a risk factor for breast cancer has been well established. A decrease in the urinary 2/16α-hydroxyestrone ratio has also been shown to be a risk marker for breast cancer. These two observations are connected by the fact that obese women have decreased levels of 2-hydroxyestrone. To test the hypothesis that fat depots secrete factors that inhibit 2-hydroxylation, the effect of substances released into the media from adipocytes incubated in Krebs-Ringer buffer, on estrogen metabolism by MCF-7 cells in minimum essential medium eagle (MEM) plus adipocyte-conditioned media (ACM) was studied. The 1:1 ACM-MEM culture system resulted in a substantial and highly significant decrease in 2-hydroxylation of estradiol. This inhibition was partially reversed by the addition of indole-3-carbinol, a potent inducer of 2-hydroxylation of estradiol. Centrifugal sizing showed that the active 2-hydroxylation inhibitor in the medium had a molecular weight of about 30 kDa. These results suggest a mechanism for the decrease in 2-hydroxylation of estradiol that is observed in obese women and the increase in 2-hydroxylation observed in women with depleted fat depots.
authors.affiliation: Strang Cancer Research Laboratory, New York, NY, USA. hlbradlow@gmail.com
authors.forename: H Leon
authors.initials: HL
authors.lastname: Bradlow
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Sepkovic
authors.forename: Nitin
authors.initials: N
authors.lastname: Telang
authors.forename: Raj
authors.initials: R
authors.lastname: Tiwari
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000032:analysis; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000378:metabolism; D006900:Hydroxylation / Q000502:physiology; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D017077:Culture Media, Conditioned; D004967:Estrogens; D006894:Hydroxyestrones; D004958:Estradiol