Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue

The study was designed to determine the process and limitations by which estrone sulfate may be a precursor of estradiol in the parenchymal cells of the normal breast. The concentration of estrone sulfate in breast nipple aspirate fluid was 1000-fold greater than that of estradiol. Concentrations of ³H-estrone sulfate in parenchymal cells were only 0.20-0.33 times that of the 1.0nM concentration in the medium, while ³H-estrone achieved concentrations up to 24 times that in the medium at 37°C. Nevertheless, estrone sulfate added to the medium was linearly converted within a 1000-fold concentration range to estrone in intact cells with a mean half-time of conversion of 628min per 10⁶ cells. Homogenized cells had a half-time of 246min per 10⁶ cells. Thus, the time for entry of estrone sulfate into cells reduced the rate by approximately 55%. In split samples, the V_max values (±S.D.) for intact and homogenized cells were 12.6±1.4 and 18.3nmol/hmg DNA, respectively (P<0.03). The corresponding K_m values for intact and homogenized cells were 6.0±1.1 and 4.7±1.0μM. Conversion of estrone sulfate to estradiol was more efficient in intact cells than in homogenates with mean half-times of 2173 and 7485min per 10⁶ cells, respectively. Conversion of estrone to estrone sulfate did not occur in these cells despite sulfonation of estrone by MCF-7 breast cancer cells under identical conditions. It is concluded that estrone sulfate can serve as a precursor for estradiol in normal breast tissue. Conversion of estrone to estradiol is a limiting step in the process.