ESTROGEN-RECEPTOR AND C-19-5-ENE-STEROID CONCENTRATIONS IN THE NUCLEAR FRACTION FROM HUMAN BREAST-CARCINOMA TISSUE

The adrenal-derived estrogen 5-androstene-3beta,17beta-diol (ADIOL) is estrogenic at the concentrations found in the blood of Western women. We have now measured the concentrations of both ADIOL and the estrogen receptor (ER) in the nuclear fraction (800 g pellet) of 89 primary human mammary tumors. No difference was found in nuclear ADIOL concentrations in tumors from 45 pre- and 44 postmenopausal women. Significantly higher nuclear ADIOL concentrations were found in 49 ER negative tumors compared to 40 ER positive tumors (P < 0.005). A similar relationship applied in the postmenopausal group (P = 0.01) and the premenopausal group, but in this latter instance failed to reach significance (P = 0.1). In ER positive tumors there was no correlation between ADIOL and ER nuclear levels. ADIOL was present in the total particulate fraction (100,000 g pellet) at twice the concentration found in the nuclear 800 g pellet and again no difference was found in its concentration in tumors from 20 pre- compared to 34 postmenopausal women. Dehydroepiandrosterone was also measured in the 800 g fraction of 45 tumors and its concentration, which was some 10-fold higher than ADIOL and significantly correlated with that steroid, was again independent of menopausal status. The higher concentration of C19-5-ene-steroids in ER negative cellular fractions could be due to differences in their metabolism; ER negative tumors either lack, or possess very low levels of, hydroxysteroid sulfotransferase which catalyzes formation of sulfate esters of C19-5-ene-steroids previously observed to be major metabolites produced by ER positive cells. Higher concentrations of free steroids in ER negative cells would then be available for combination with membranes and non-specific binding sites throughout the cell.