Qualitative and quantitative differences in estrogen biotransformation in human breast glandular and adipose tissues: implications for studies using mammary biospecimens
Qualitative and quantitative differences in estrogen biotransformation in human breast glandular and adipose tissues: implications for studies using mammary biospecimens
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人乳腺和脂肪组织中雌激素生物转化的定性和定量差异：对使用乳腺生物样本的研究的影响
DOI：
10.1007/s00204-019-02564-w
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发表时间：
2019
影响因子：
6.1
通讯作者：
L. Lehmann
中科院分区：
文献类型：
--
作者：
Daniela Pemp;Carolin Kleider;Katja Schmalbach;R. Hauptstein;Leo N. Geppert;Claudia Köllmann;K. Ickstadt;P. Eckert;I. Neshkova;R. Jakubietz;Harald L. Esch;L. Lehmann
由于雌激素在乳腺癌病因学中的作用，几十年来，人们一直在研究雌激素的生物转化(及其化合物与其相互作用)。然而，人们很少注意到这样一个众所周知的事实，即乳腺腺(GLT)和脂肪(ADT)组织的比例存在较大的个体间差异，并且较少考虑适当的组织特征。为了评估这一点的相关性，本研究比较了GLT和ADT中雌激素的生物转化。GLT和ADT是从47例来自非乳腺癌女性的乳房缩小术标本中分离出来的，并通过组织学和含油率进行了表征。分别用GC-MS和UHPLC-MS/MS分析了12种非结合雌激素和5种结合雌激素的水平，并用Taqman®探针为基础的聚合酶链式反应分析了参与雌激素生物转化的27个转录本的水平。出乎意料的是，三分之一的标本只有在冷冻后才能提供整齐的GLT。17个β-雌二醇、雌酮和雌酮-3-硫酸酯在两种组织中均检测到，而雌酮-3-葡萄糖醛酸苷和2-甲氧基雌酮分别在GLT和ADT中检测到。雌激素水平以及17β-雌二醇/雌酮和雌酮-3-硫酸酯/雌酮在两组间有显著差异，但小于个体间。此外，GLT和ADT中的雌激素水平彼此显著相关。相比之下，参与生物转化的大多数编码酶的转录本的水平比个体之间的差异更大，而且ADT和GLT之间没有相关性。因此，混合的乳腺组织(和血浆)不会提供关于局部雌激素生物转化(以及化合物与其相互作用)的有意义的信息，而17个β-雌二醇水平的相对变化可能在更丰富的ADT中被研究。
Because of its assumed role in breast cancer etiology, estrogen biotransformation (and interaction of compounds therewith) has been investigated in human biospecimens for decades. However, little attention has been paid to the well-known fact that large inter-individual variations exist in the proportion of breast glandular (GLT) and adipose (ADT) tissues and less to adequate tissue characterization. To assess the relevance of this, the present study compares estrogen biotransformation in GLT and ADT. GLT and ADT were isolated from 47 reduction mammoplasty specimens derived from women without breast cancer and were characterized histologically and by their percentages of oil. Levels of 12 unconjugated and five conjugated estrogens were analyzed by GC- and UHPLC–MS/MS, respectively, and levels of 27 transcripts encoding proteins involved in estrogen biotransformation by Taqman® probe-based PCR. Unexpectedly, one-third of specimens provided neat GLT only after cryosection. Whereas 17β-estradiol, estrone, and estrone-3-sulfate were detected in both tissues, estrone-3-glucuronide and 2-methoxy-estrone were detected predominately in GLT and ADT, respectively. Estrogen levels as well as ratios 17β-estradiol/estrone and estrone-3-sulfate/estrone differed significantly between GLT and ADT, yet less than between individuals. Furthermore, estrogen levels in GLT and ADT correlated significantly with each other. In contrast, levels of most transcripts encoding enzymes involved in biotransformation differed more than between individuals and did not correlate between ADT and GLT. Thus, mixed breast tissues (and plasma) will not provide meaningful information on local estrogen biotransformation (and interaction of compounds therewith) whereas relative changes in 17β-estradiol levels may be investigated in the more abundant ADT.
影响因子：
9.8
作者：
Zhang, Yan;Gaikwad, Nilesh W.;Rogan, Eleanor G.
通讯作者：
Rogan, Eleanor G.
雌激素代谢和乳腺癌。
影响因子：
9.7
作者：
Samavat H;Kurzer MS
通讯作者：
Kurzer MS
影响因子：
5.8
作者：
Rosner, William;Hankinson, Susan E.;Wierman, Margaret E.
通讯作者：
Wierman, Margaret E.