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Pharmacol Res. 2016 Apr;106:114-122. doi: 10.1016/j.phrs.2016.02.021. Epub 2016 Feb 27.

New insights into the androgen biotransformation in prostate cancer: A regulatory network among androgen, androgen receptors and UGTs.

Author information

1
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
2
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, TX, USA.
3
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: usxinwang@gmail.com.

Abstract

Androgen, as one kind of steroid hormones, is pivotal in the hormone-sensitive cancer, such as prostate cancer (PCa). The synthesis, elimination, and bioavailability of androgen in prostate cells have been proved to be a main cause of the carcinogenesis, maintenance and deterioration of PCa. This review illustrates the outlines of androgen biotransformation, and further discusses the different enzymes, especially UDP-glucuronyltransferases (UGTs) embedded in both benign and malignant prostate cells, which catalyze the reactions. Although many inhibitors of the enzymes responsible for the synthesis of androgens have been developed into drugs to fight against PCa, the elimination procedures metabolized by the UGTs are less emphasized. Thus the regulatory network among androgen, androgen receptors (AR) and UGTs is carefully reviewed in this article, indicating the determinant effects of UGTs on prostatic androgens and the regulation of AR. Finally, the hypothesis is also put forward that the regulators of UGTs may be developed to accelerate the androgen elimination and benefit PCa therapy.

KEYWORDS:

Abiraterone acetate (PubChem CID: 57336518); Androgen; Androgen receptors; Androsterone (PubChem CID: 5879); Bicalutamide (PubChem CID: 2375); Biotransformation; Dehydroepiandrosterone (PubChem CID: 5881); Dihydrotestosterone (PubChem CID: 10635); Dutasteride (PubChem CID: 6918296); Enzalutamide (PubChem CID: 15951529); Finasteride (PubChem CID: 57363); Flutamide (PubChem CID: 3397); Orteronel (PubChem CID: 9796590); Prostate cancer; Testosterone (PubChem CID: 6013); UDP-glucuronyltransferases

PMID:
26926093
DOI:
10.1016/j.phrs.2016.02.021
[Indexed for MEDLINE]

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