Expression of transcripts encoding steroid UDP-glucuronosyltransferases in human prostate hyperplastic tissue and the LNCaP cell line.
The UDP-glucuronosyltransferase (EC 2.4.1.17) enzymes transform many lipophilic compounds to more water-soluble products via conjugation with glucuronic acid. This conversion is responsible for enhancing the excretion of endogenous aglycones such as steroids. To date, several distinct isoforms of steroid UDP-glucuronosyltransferases (UGTs) have been isolated in the human liver. Among these UGTs, UGT2B7 is specific for estriol and 3,4-catechol estrogens, UGT2B15 glucuronidates 17beta-hydroxy-C19 steroids while UGT2B10 has as yet an undescribed activity. To further demonstrate the presence of UGTs in peripheral tissues we studied the expression of these enzymes in human prostate hyperplastic tissue and the LNCaP cell line. Metabolism studies using intact LNCaP cells in culture indicate the presence of UGT activities involved in the glucuronidation of 3alpha-hydroxysteroids (androsterone) and 17beta-hydroxysteroids (testosterone and dihydrotestosterone). Northern blot analysis of poly(A+) RNA from LNCaP cells and prostate using a UGT2B15 cDNA probe revealed two bands of 2.0 and 2.3 kb. In order to identify more specifically the mRNAs detected in Northern blot analysis we used RNase protection and RT-PCR, although, these approaches did not allow detection of UGT2B7 transcripts. Our studies demonstrate the presence of two UGT activities and at least two types of UGT transcripts in both the human prostate and the LNCaP.
Bélanger
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MRC Group in Molecular Endocrinology, CHUL Research Center, Québec, Canada.
Beaulieu
M
M
Marcotte
B
B
Lévesque
E
E
Guillemette
C
C
Hum
D W
DW
Bélanger
A
A
D000738:Androsterone / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D015342:DNA Probes; D013196:Dihydrotestosterone / Q000378:metabolism; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D011467:Prostate / Q000201:enzymology; D011470:Prostatic Hyperplasia / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D013256:Steroids / Q000378:metabolism*; D013379:Substrate Specificity; D013739:Testosterone / Q000378:metabolism
D015342:DNA Probes; D012333:RNA, Messenger; D013256:Steroids; D013196:Dihydrotestosterone; D013739:Testosterone; D000738:Androsterone; D014453:Glucuronosyltransferase