A. Radominskapandya et al., UDP-GLUCURONOSYLTRANSFERASES IN HUMAN INTESTINAL-MUCOSA, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1394(2-3), 1998, pp. 199-208
While UDP-glucuronosyltransferases (UGTs) are known to be expressed at
high levels in human liver, relatively little is known about extrahep
atic expression. In the present study, UGT2B family isoforms involved
in the glucuronidation of steroid hormones and bile acids have been ch
aracterized in microsomes prepared from jejunum, ileum and colon from
six human subjects. Glucuronidation of androsterone and testosterone w
as highly significant and increased from proximal to distal intestine.
In contrast, hyodeoxycholic acid was glucuronidated at a low level in
jejunum and ileum and activity was barely detectable in colon. No sig
nificant glucuronidation of lithocholic acid was found. Small phenols
were glucuronidated with much lower activity than found in liver. High
levels of UGT protein were detected with polyclonal anti-rat androste
rone- and testosterone-UGT antibodies, whereas UGT2B4, a major hepatic
hyodeoxycholic acid-specific UGT, was undetectable using a highly spe
cific anti-human UGT2B4 antibody. Screening for RNA expression by RT-P
CR confirmed the absence of UGT2B4 and UGT1A6 and showed expression of
UGT2B7, a hepatic isoform shown to glucuronidate androsterone, in all
intestinal segments. To our knowledge, the presence of functional and
rosterone and testosterone directed isoforms in human intestine is a n
ovel finding which supports the idea that the intestinal tract functio
ns as a steroid-metabolizing organ and plays a significant role in ste
roid hormone biotransformation. (C) 1998 Published by Elsevier Science
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