Qualitative and quantitative differences in estrogen biotransformation in human breast glandular and adipose tissues: implications for studies using mammary biospecimens

  • Daniela Pemp
  • Carolin Kleider
  • Katja Schmalbach
  • René Hauptstein
  • Leo N. Geppert
  • Claudia Köllmann
  • Katja Ickstadt
  • Peter Eckert
  • Iva Neshkova
  • Rafael Jakubietz
  • Harald L. Esch
  • Leane LehmannEmail author
Toxicokinetics and Metabolism


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.


Estradiol Biotransformation Tissue levels Breast adipose tissue Breast glandular tissue 



This work is part of the joint research project, IsoCross, entitled “Isoflavones: Cross-species comparison of metabolism, estrogen sensitivity, epigenetics and carcinogenesis”, which was supported in whole by the German Research Foundation to L. Lehmann (DFG LE 1329/10-1). The authors are indebted to Dr. Ulrike Waldhofen (mammoplasty specimen), Anne Scheffler (assistance during manuscript preparation), Ben Spielmann (help with sample collection, cryosection, microscopy and data administration), Sabine Winkler (help with analysis of estrogen conjugates), and Harald Schuchardt, Ersan Elemen, Thomas Kunz, Maryam Mahdiani (help with cryosection) as well as to Prof. Günter Vollmer (discussion of the manuscript).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

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Supplementary material 5 (PDF 114 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Chair of Food Chemistry, Institute of Pharmacy and Food ChemistryUniversity of WürzburgWürzburgGermany
  2. 2.Chair of Mathematical Statistics with Applications in BiometricsTU Dortmund UniversityDortmundGermany
  3. 3.Clinic for Plastic and Aesthetic SurgeryWürzburgGermany
  4. 4.Department of Trauma, Hand, Plastic and Reconstructive SurgeryUniversity Hospital WürzburgWürzburgGermany

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