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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Penning, T.M. et al.

Trevor M. Penning, Yi Jin, Tea Lanisnik Rizner, David R. Bauman,

Pre-receptor regulation of the androgen receptor.

The human androgen receptor (AR) is a ligand-activated nuclear transcription factor and mediates the induction of genes involved in the development of the male phenotype and male secondary sex characteristics, as well as the normal and abnormal growth of the prostate. We have identified the pair of hydroxysteroid dehydrogenases (HSDs) that regulate ligand access to the AR in human prostate. We find that type 3 3alpha-HSD (aldo-keto reductase (AKR)1C2) catalyzes the NADPH dependent reduction of the potent androgen 5alpha-dihydrotestosterone (5alpha-DHT) to yield the inactive androgen 3alpha-androstanediol (3alpha-diol). We also find that RoDH like 3alpha-HSD (RL-HSD) catalyzes the NAD(+) dependent oxidation of 3alpha-diol to yield 5alpha-DHT. Together these enzymes are involved in the pre-receptor regulation of androgen action. Inhibition of AKR1C2 would be desirable in cases of androgen insufficiency and inhibition of RL-HSD might be desirable in benign prostatic hyperplasia.[1]

References

Pre-receptor regulation of the androgen receptor. Penning, T.M., Jin, Y., Rizner, T.L., Bauman, D.R. Mol. Cell. Endocrinol. (2008) [Pubmed]

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