5α-reductase types I and II are important in conversion of testosterone to dihydrotestosterone and target in the treatment of BPH. 5α-reductase-3 was identified by mining the Human Genome Project database. These investigators sought to analyze the expression of 5α-reductase-3 in human tissues with emphasis during prostate carcinogenesis and progression.
They found 5α-reductase-3 expression at the mRNA level was increased in CaP cell lines compared to benign prostate cell lines. Results however varied with regard to immunoreactivity at the protein level. High levels of 5α-reductase-3 were found in some benign human tissues to include skin, kidney, liver, skeletal muscle myometrium and pancreas. 5α-reductase-3 was usually within the cytoplasm, but with intense expression, perinuclear localization was also seen. In malignant tissues, there was variation between organs and patients. Only malignant breast, testis, lung, and thyroid tissues had clear expression compared to their benign counterpart tissues. Studies in prostate tissues suggest that 5α-reductase-3 expression is in the basal cell compartment. Low levels were observed in luminal epithelial cells. In high grade PIN, staining of 5α-reductase-3 was found in both basal cells and luminal epithelial cells. The immunostaining of 5α-reductase-3 had similar cytoplasmic intensity in androgen-stimulated and castration-resistant CaP. The 5α-reductase-3 staining was confirmed by co-localization with AMACR. The further understanding of 5α-reductase-3 in CaP may hold clues regarding androgen regulation.
Godoy A, Kawinski E, Li Y, Oka D, Alexiev B, Azzouni F, Titus MA, Mohler JL
Prostate. 2010 Dec 28. Epub ahead of print.