title: Expression of UDP-glucuronosyltransferase 1A4 in human placenta at term.
abstract: The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure control. The placenta may be involved in this. Microsomes from term placentas of 4 LTG-users and 10 healthy control subjects were prepared. Western blot analysis detected UGT1A proteins in all placentas. The presence of UGT1A4 in placenta from LTG users was confirmed with UGT1A4 commercial standard and a specific UGT1A4 primary antibody. Since LTG is primarily metabolized by UGT1A4 and this isozyme is shown to be present in placenta at term, it may be hypothesized that the placenta is involved in the fall of LTG serum concentrations during pregnancy.
authors.affiliation: Department of Clinical Pharmacology, St. Olavs University Hospital, and Department of Neuroscience, Faculty of Medicine, NTNU, P. O. Box 3250 Sluppen, 7006, Trondheim, Norway. arne.reimers@legemidler.no
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.forename: Lene
authors.initials: L
authors.lastname: Østby
authors.forename: Ina
authors.initials: I
authors.lastname: Stuen
authors.forename: Eirik
authors.initials: E
authors.lastname: Sundby
mesh_terms: D000927:Anticonvulsants / Q000493:pharmacokinetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000077213:Lamotrigine; D008861:Microsomes / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D014227:Triazines / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase; D000077213:Lamotrigine