Novel insight in estrogen homeostasis and bioactivity in the ACI rat model of estrogen-induced mammary gland carcinogenesis

Pemp, Daniela; Esch, Harald L.; Hauptstein, René; Möller, Frank; Zierau, Oliver; Bosland, Maarten C.; Geppert, Leo N.; Kleider, Carolin; Schlereth, Katharina; Vollmer, Günter; Lehmann, Leane

doi:10.1007/s00204-019-02483-w

Cited by 2 publications

(2 citation statements)

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“…Further supporting the role of intratissue biotransformation, levels of E2 and of E1 in ADT were also significantly influenced by levels of HSD17B2. Recently, it was shown that levels of Hsd17b enzymes significantly influenced intramammary levels of E2 in the ACI rat model of tumorigenesis (Pemp et al 2019b), as well, supporting the important role of HSD17Bs in intramammary estrogen homeostasis (Hilborn et al 2017) across species.…”

Section: Relevancementioning

confidence: 85%

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

et al. 2020

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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 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.

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Section: Relevancementioning

confidence: 85%

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

et al. 2020

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“…4,4-Disubstituted and allyl substituted alkenes ( 2i – 2l ) generally showed an increased ratio of linear/branch products containing an ester ( 2j ) and other functionalities with satisfactory yield and up to 95% linear selectivity ( 2i ). Biologically active substrates also reacted to afford the corresponding alkylation products ( 2m and 2n ). Vinylcyclohexene was one of the more suitable alkenes for this reaction, providing 2o in high yield and with high selectivity.…”

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confidence: 99%

Rh(II)-Catalyzed C–H Alkylation of Benzylamines with Unactivated Alkenes: The Influence of Acid on Linear and Branch Selectivity

Das

Chatani

2021

Org. Lett.

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The Rh-catalyzed C−H alkylation of benzylamine derivatives with unactivated 1-alkenes that proceeds via a picolinamide directing group is reported. The crucial role of an acid additive in this transformation is confirmed. Aromatic acids showed high linear selectivity, and aliphatic acids provided branched alkylation products as the major product. The reaction has a broad scope for benzylamines and alkenes. Deuterium labeling experiments suggest that a Rh-carbene intermediate is involved in the case of linear product formation. A different reaction pathway, however, appears to be involved in the case of branched alkylation products, and this pathway also appeared to be a minor pathway in linear-selective reactions.

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Novel insight in estrogen homeostasis and bioactivity in the ACI rat model of estrogen-induced mammary gland carcinogenesis

Cited by 2 publications

References 49 publications

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

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

Rh(II)-Catalyzed C–H Alkylation of Benzylamines with Unactivated Alkenes: The Influence of Acid on Linear and Branch Selectivity

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