U-shaped microRNA expression pattern could be a new concept biomarker for environmental estrogen

Abstract

Estrogen regulates miRNA expression in a typical U-shaped dose-response pattern.

E2 can regulate drosha in the ventral prostate.

Mouse ventral prostate is most sensitive to estrogen.

Nonmonotonic dose-response in prostate could be a component of estrogen signature.

Many studies have focused on environmental estrogen-related diseases. However, no consistent gene markers or signatures for estrogenicity have been discovered in mammals. This study investigated the estrogenic effects of 17β-estradiol on the prostate in immature male mice. Consistent U-shaped responses were seen in bodyweight, ventral prostate epithelial morphology, and miRNA expression levels. Specifically, most estradiol regulated miRNAs were downregulated at low doses of estradiol (0.2 and 2 mg·kg⁻¹), and whose expression returned to the control level at a larger dose (200 mg·kg⁻¹). The function of these regulated miRNAs is related to the prostate cancer and PI3K-Akt signaling pathways, which is consistent with the function of estradiol. Furthermore, the miRNA-processing machinery, Drosha, in the prostate was also regulated in a similar pattern, which could be a part of the U-shaped miRNA expression mechanism. All of these data indicate that the prostate is a reliable organ for evaluating estrogenic activity and that the typical nonmonotonic dose-response relationship could be used as a novel biomarker for estrogenicity.

Graphical abstract

Keywords

miRNA / Prostate / Estradiol / Nonmonotonic dose-response / Estrogenicity / Drosha

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 21377066 and 21007030).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11783-016-0880-8 and is accessible for authorized users.

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2016 Higher Education Press and Springer-Verlag Berlin Heidelberg