Presence of 5alpha-reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue.
BACKGROUND
Prostate trophism depends on DHT formed from T by the enzyme 5alpha-R. Two 5alpha-R isoforms with different biochemical characteristics have been cloned. Also estrogens might contribute to the prostate growth; however, their intraglandular formation by the enzyme aromatase is still debated. The aim of the present study was to verify whether (a) only one or both isoforms of the 5alpha-Rs are expressed in the prostate cancer cell line LNCaP and in BPH, or (b) the aromatase is present in these samples.


METHODS
The profile of the pH optimum of the 5alpha-Rs was evaluated "in vitro" in LNCaP cells by the production of labeled 5alpha-reduced metabolites either from [14C]-T or [14C]-D4 at pH 3.5-8. The gene expression of the two 5alpha-Rs and of the aromatase in LNCaP cells and in BPH specimens was analyzed by RT-PCR combined to Southern blot analysis, using specific sets of oligonucleotides. The tissue localization of 5alpha-R1 was analyzed by immunohistochemistry using an anti-5alpha-R1 polyclonal antibody.


RESULTS
(a) In LNCaP cells, the formation of 5alpha-reduced metabolites from the respective precursors increases progressively as a function of pH, being the highest at neutral pH values; (b) the 5alpha-R1 isoform is expressed in both LNCaP cells and in BPH, while the 5alpha-R2 mRNA is present only in BPH, but not in LNCaP cells; and (c) no aromatase transcripts were observed either in BPH or in LNCaP cells.


CONCLUSIONS
A careful examination of the possible differential expression of T-activating enzymes, particularly in prostate cancer, would be of help to choose the appropriate treatment.
Negri-Cesi
P
P
Center for Endocrinological Oncology, Department of Endocrinology, University of Milano, Italy. pnc@imiuccd.csi.unimi.it
Poletti
A
A
Colciago
A
A
Magni
P
P
Martini
P
P
Motta
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011817:Rabbits; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase