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

Formation of estrone and estradiol from estrone sulfate by normal breast parenchymal tissue
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DOI:
10.1016/s0960-0760(03)00266-8
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发表时间:
2003-08-01
影响因子:
4.1
通讯作者:
Khan, SA
Khan, SA
中科院分区:
生物学2区
文献类型:
--
作者:
Chatterton, RT;Geiger, AS;Khan, SA

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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 H-3-estrone sulfate in parenchymal cells were only 0.20-0.33 times that of the 1.0 nM concentration in the medium, while H-3-estrone achieved concentrations up to 24 times that in the medium at 37 degreesC. 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 V-max 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 K-m values for intact and homogenized cells were 6.0 +/- 1.1 and 4.7 +/- 1.0 muM. 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. (C) 2003 Elsevier B.V. All rights reserved.