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

Robert T. Chatterton*, Angela S. Geiger, Peter H. Gann, Seema A. Khan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 Vmax values (±S.D.) for intact and homogenized cells were 12.6±1.4 and 18.3nmol/hmg DNA, respectively (P<0.03). The corresponding Km 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.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume86
Issue number2
DOIs
StatePublished - Aug 2003

Keywords

  • Estradiol
  • Estrone
  • Estrone sulfate
  • Nipple aspirate fluid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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