Endogenous Concentration and Subcellular Distribution of Estrogens in Normal and Malignant Human Breast Tissue

The endogenous concentrations and the subcellular distribution of dehydroepiandrosterone (DHEA) and 5-androstene-3β,17β-diol (ADIOL) were measured in malignant and nonmalignant human breast tissue from both pre- and postmenopausal women. DHEA 3-sulfate was measured only in the cytosol. A greater tissue-plasma gradient of DHEA was present with large variations. The highest concentration of DHEA and ADIOL occurred in the nuclear fraction (average, 2.9 and 1.6 times the concentration in cytosol). With respect to DHEA, this finding is remarkable because no specific binding protein in human breast tissue has been reported. The concentration of DHEA 3-sulfate was significantly higher in the cytosol of nonmalignant than in malignant breast tissues. No significant differences in tissue concentrations of DHEA and ADIOL were found in malignant and nonmalignant breast tissue. The concentration of estrogens was measured in the cytosol and the nuclear fraction of the same tissues, as reported in a previous paper. We found a significantly higher estradiol concentration in malignant tissue as compared to nonmalignant tissue. When the ratio of ADIOL to estradiol was calculated from the combined data, a significant difference was found only in the cytosol of premenopausal cancer patients versus normal women. No difference was seen in the postmenopausal women. No difference in the ADIOL:estradiol ratio was found between normal and malignant breast tissue of patients of the same menopausal status.