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Influence of breast cancer risk factors and intramammary biotransformation on estrogen homeostasis in the human breast

Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-235335
  • Understanding intramammary estrogen homeostasis constitutes the basis of understanding the role of lifestyle factors in breast cancer etiology. Thus, the aim of the present study was to identify variables influencing levels of the estrogens present in normal breast glandular and adipose tissues (GLT and ADT, i.e., 17β-estradiol, estrone, estrone-3-sulfate, and 2-methoxy-estrone) by multiple linear regression models. Explanatory variables (exVARs) considered were (a) levels of metabolic precursors as well as levels of transcripts encodingUnderstanding intramammary estrogen homeostasis constitutes the basis of understanding the role of lifestyle factors in breast cancer etiology. Thus, the aim of the present study was to identify variables influencing levels of the estrogens present in normal breast glandular and adipose tissues (GLT and ADT, i.e., 17β-estradiol, estrone, estrone-3-sulfate, and 2-methoxy-estrone) by multiple linear regression models. Explanatory variables (exVARs) considered were (a) levels of metabolic precursors as well as levels of transcripts encoding proteins involved in estrogen (biotrans)formation, (b) data on breast cancer risk factors (i.e., body mass index, BMI, intake of estrogen-active drugs, and smoking) collected by questionnaire, and (c) tissue characteristics (i.e., mass percentage of oil, oil%, and lobule type of the GLT). Levels of estrogens in GLT and ADT were influenced by both extramammary production (menopausal status, intake of estrogen-active drugs, and BMI) thus showing that variables known to affect levels of circulating estrogens influence estrogen levels in breast tissues as well for the first time. Moreover, intratissue (biotrans)formation (by aromatase, hydroxysteroid-17beta-dehydrogenase 2, and beta-glucuronidase) influenced intratissue estrogen levels, as well. Distinct differences were observed between the exVARs exhibiting significant influence on (a) levels of specific estrogens and (b) the same dependent variables in GLT and ADT. Since oil% and lobule type of GLT influenced levels of some estrogens, these variables may be included in tissue characterization to prevent sample bias. In conclusion, evidence for the intracrine activity of the human breast supports biotransformation-based strategies for breast cancer prevention. The susceptibility of estrogen homeostasis to systemic and tissue-specific modulation renders both beneficial and adverse effects of further variables associated with lifestyle and the environment possible.zeige mehrzeige weniger

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Autor(en): Daniela Pemp, Leo N. Geppert, Claudia Wigmann, Carolin Kleider, René Hauptstein, Katja Schmalbach, Katja Ickstadt, Harald L. EschORCiD, Leane LehrmannORCiD
URN:urn:nbn:de:bvb:20-opus-235335
Dokumentart:Artikel / Aufsatz in einer Zeitschrift
Institute der Universität:Fakultät für Chemie und Pharmazie / Institut für Pharmazie und Lebensmittelchemie
Sprache der Veröffentlichung:Englisch
Titel des übergeordneten Werkes / der Zeitschrift (Englisch):Archives of Toxicology
ISSN:0340-5761
Erscheinungsjahr:2020
Band / Jahrgang:94
Seitenangabe:3013–3025
Originalveröffentlichung / Quelle:Archives of Toxicology (2020) 94:3013–3025. https://doi.org/10.1007/s00204-020-02807-1
DOI:https://doi.org/10.1007/s00204-020-02807-1
Allgemeine fachliche Zuordnung (DDC-Klassifikation):5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Freie Schlagwort(e):estrogens; human breast; multiple linear regression
Datum der Freischaltung:23.06.2021
Lizenz (Deutsch):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International