Molecular expression of 17 βhydroxysteroid dehydrogenase types in relation to their activity in intact human prostate cancer cells

Abstract

In the present study we have inspected estrogen metabolism in cultured human prostate cancer cells (LNCaP, DU145, PC3), in relation to the expression of mRNAs for different 17 βhydroxysteroid dehydrogenase (17 βHSD) enzymes (from 1 to 4). Using an intact cell analysis, we have compared precursor degradation and product formation after incubation of cells with physiological amounts of radioactive E 2 or estrone (E 1) for 24–72 h and subsequent reverse-phase high performance liquid chromatography analysis. The LNCaP and DU145 cells only partly converted E 2 to E 1 (26 and 13% at 72 h, respectively), giving rise to an appreciable production of E 2 from E 1 (nearly 20% in all cases). Conversely, PC3 cells revealed a massive E 2 oxidation to E 1 (up to 90% by 72 h) and a scant formation of E 2 (<2%) from E 1. In addition, an appreciable formation of 16 αOHE 1 was seen in either PC3 (11%) or DU145 (5%) cells, respectively using E 2 or E 1 as precursor. All three cell lines exhibited marked amounts of 17 βHSD4 mRNA species, whilst even greater amounts of 17 βHSD2 transcript were found in PC3 cells only. No mRNA for either 17 βHSD1 or 17 βHSD3 could be detected in any cell line. The present evidence indicates that pathways of estrogen metabolism are distinctly governed in prostate cancer cells depending on their endocrine status, being associated with a differential expression of mRNA for different 17 βHSD enzymes.