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(Received for publication, March 11, 1996, and in revised form, May 13, 1996)
From the Medical Research Council Group in Molecular Endocrinology,
CHUL Research Center, Laval University,
Québec G1V 4G2, Canada
To isolate cDNA clones encoding novel UGT2B
enzymes, human prostate and LNCaP cell cDNA libraries were screened
using a pool of steroid-specific UGT2B cDNA probes. In
approximately 106 recombinants, we isolated 3 cDNA
clones of 2.1 kilobases that encode a novel UGT2B enzyme. UGT2B17 is
95% identical with UGT2B15 and 91% identical with UGT2B8. Primary
structure analysis of UGT2B17 based on the nucleotide sequence revealed
a putative amino-terminal membrane insertion signal peptide, a
carboxyl-terminal membrane-spanning region, and three potential
asparagine-linked glycosylation sites. UGT2B17 cloned in the pBK-CMV
expression vector was transfected into HK293 cells to obtain a stable
clonal cell line expressing a high level of the active 53-kDa UGT2B17
enzyme. Of the over 60 endogenous and exogenous substances tested, 25 compounds revealed reactivity. The major substrates are eugenol > 4-methylumbelliferone > dihydrotestosterone > androstane-3
Volume 271, Number 37,
Issue of September 13, 1996
pp. 22855-22862
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,17
-diol (3-diol) > testosterone > androsterone (ADT). The apparent Km values obtained
with tritiated steroids in intact cells were 0.4 µM for
ADT, 0.7 µM for dihydrotestosterone, 1.0 µM
for 3-diol, and 3.4 µM for testosterone. Southern blot
analysis of reverse transcription-polymerase chain reaction products
revealed expression of UGT2B17 mRNA in various tissues including
the liver, kidney, testis, uterus, placenta, mammary gland, adrenal
gland, skin, and prostate. UGT2B17 is the first human uridine
diphosphoglucuronosyltransferase enzyme expressed in extrahepatic
tissues to have a specificity for ADT as well as testosterone,
dihydrotestosterone, and 3-diol.
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