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Review
. 2009 Feb:1155:33-42.
doi: 10.1111/j.1749-6632.2009.03700.x.

Steroid hormone transforming aldo-keto reductases and cancer

Trevor M Penning  1 , Michael C Byrns
Affiliations
Review

Steroid hormone transforming aldo-keto reductases and cancer

Trevor M Penning et al. Ann N Y Acad Sci. 2009 Feb.

Abstract

Prostate and breast cancer are hormone-dependent malignancies of the aging male and female and require the local production of androgens and estrogens to stimulate cell proliferation. Aldo-keto reductases (AKR) play key roles in this process. In the prostate, AKR1C3 (type 5 17beta-HSD) reduces Delta(4)-androstene-3,17-dione to yield testosterone while AKR1C2 (type 3 3alpha-HSD) eliminates 5alpha-dihydrotestosterone (5alpha-DHT), and AKR1C1 forms 3beta-androstanediol (a ligand for ERbeta). In the breast, AKR1C3 forms testosterone, which is converted to 17beta-estradiol by aromatase or reduces estrone to 17beta-estradiol directly. AKR1C3 also acts as a prostaglandin (PG) F synthase and forms PGF(2alpha) and 11beta-PGF(2alpha), which stimulate the FP receptor and prevent the activation of PPARgamma by PGJ(2) ligands. This proproliferative signaling may stimulate the growth of hormone-dependent and -independent prostate and breast cancer.

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Figures

Figure 1
Figure 1
Central role of human AKR1C enzymes in androgen metabolism in the prostate; AR, androgen receptor; ERβ, estrogen receptor.
Figure 2
Figure 2
Role of AKR1C3 in the local production of 17β-estradiol in the breast.
See this image and copyright information in PMC

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