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 1.0 nM concentration in the medium, while 3H-estrone achieved concentrations up to 24 times that in the medium at 37 degrees 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 628 min per 10(6) cells. Homogenized cells had a half-time of 246 min per 10(6) cells. Thus, the time for entry of estrone sulfate into cells reduced the rate by approximately 55%. In split samples, the Vmax values (+/- S.D.) for intact and homogenized cells were 12.6 +/- 1.4 and 18.3 nmol/h mg DNA, respectively (P<0.03). The corresponding Km values for intact and homogenized cells were 6.0 +/- 1.1 and 4.7 +/- 1.0 microM. Conversion of estrone sulfate to estradiol was more efficient in intact cells than in homogenates with mean half-times of 2173 and 7485 min per 10(6) 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.
Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, 710 N Fairbanks Court, Chicago, IL 60611, USA. chat@northwestern.edu
Robert T
RT
Chatterton
Angela S
AS
Geiger
Peter H
PH
Gann
Seema A
SA
Khan
D000328:Adult; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis*; D004970:Estrone / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008597:Menstrual Cycle; D017697:Premenopause; D014316:Tritium
D014316:Tritium; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate