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UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term
Abby C Collier1, Natalie A Ganley, Malcolm D Tingle
1Department of Pharmacology and Clinical Pharmacology, University of Auckland Medical School, Private Bag 92019 Auckland, New Zealand. a.collier@auckland.ac.nz
Biochemical Pharmacology
|February 21, 2002
Summary
Human placental UDP-glucuronosyltransferases (UGTs) show variable activity and expression, particularly UGT2B isoforms. These enzymes are located in placental trophoblasts, suggesting a role in detoxification and hormone regulation at the maternal-fetal interface.
Area of Science:
- Pharmacology
- Biochemistry
- Human Physiology
Background:
- UDP-glucuronosyltransferases (UGTs) are crucial enzymes for metabolizing endogenous and exogenous compounds.
- Their role and expression in the human placenta, a key site of maternal-fetal exchange, are not fully elucidated.
Purpose of the Study:
- To investigate the activity, expression, and localization of UGTs in the human placenta at term.
- To determine the specific UGT isoforms present and their functional significance.
Main Methods:
- UGT activity was measured using 4-methylumbelliferone (4-MU) as a substrate.
- UGT isoform expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting.
- Protein presence and localization were assessed using Western blotting, immunohistochemistry, and in situ hybridization.
Main Results:
- Significant inter-individual variability in UGT activity (Vmax and Km) was observed.
- Expression of UGT2B isoforms (UGT2B4, 2B7, 2B10, 2B11, 2B15, and UGT2B17) was detected in placental tissues.
- UGT2B4 and UGT2B7 proteins were localized to the syncytium of placental trophoblasts, the primary site of maternal-fetal exchange.
Conclusions:
- UGTs, particularly UGT2B isoforms, are actively expressed and functional in the term human placenta.
- Their presence at the maternal-fetal interface suggests a role in the detoxification of xenobiotics and endogenous substances.
- UGTs may also contribute to maintaining placental function through the regulation of steroid hormone levels.