PMID- 12351530
OWN - NLM
STAT- MEDLINE
DCOM- 20030304
LR  - 20190513
IS  - 0268-1161 (Print)
IS  - 0268-1161 (Linking)
VI  - 17
IP  - 10
DP  - 2002 Oct
TI  - Metabolizing enzyme localization and activities in the first trimester human 
      placenta: the effect of maternal and gestational age, smoking and alcohol 
      consumption.
PG  - 2564-72
AB  - BACKGROUND: The rationale for this study was to assess the expression, activity 
      and localization of the enzymes uridine diphosphate glucuronosyltransferase 
      (UGT), beta-glucuronidase, cytochrome P450 1A (CYP1A) and cytochrome P450 2E1 
      (CYP2E1) in first trimester human placenta and to gauge the effects of maternal 
      variables on placental metabolism. METHODS: CYP1A, CYP2E1, UGT and 
      beta-glucuronidase activities were assessed in 25 placentas using 
      ethoxyresorufin, chlorzoxazone, 4-methylumbelliferone and 4-methylumbelliferone 
      glucuronide respectively. Protein expression and localization were detected by 
      immunoblot and immunohistochemistry. All statistics were non-parametric. RESULTS: 
      UGT, beta-glucuronidase and CYP1A activities were detected in all placentas 
      sampled; CYP2E1 was undetectable. CYP1A, UGT1A UGT2B proteins were detected in 
      all placentas (n = 6) tested and CYP2E1 in 4/6 placentas sampled and were 
      localized to the syncytium. UGT and CYP1A activities were significantly elevated 
      in the placentas of mothers who smoked (P < 0.05 and P < 0.001 respectively) and 
      were greatest in women who both smoked and drank alcohol (P < 0.05 and P < 0.01 
      respectively). Enzyme activities were significantly negatively correlated with 
      gestational age (P < 0.05, r = 0.54, UGT) and maternal age respectively (P < 
      0.001, r = 0.63, CYP1A). beta-Glucuronidase activity did not differ with patient 
      variables. CONCLUSIONS: Metabolism of compounds by the human placenta in the 
      first trimester may be affected by maternal and environmental factors altering 
      the activity of constitutive metabolizing enzymes.
FAU - Collier, Abby C
AU  - Collier AC
AD  - Department of Pharmacology Clinical Pharmacology and The Liggins Institute, 
      University of Auckland, Private Bag 92019, New Zealand. abbyc@unr.edu
FAU - Tingle, Malcolm D
AU  - Tingle MD
FAU - Paxton, James W
AU  - Paxton JW
FAU - Mitchell, Murray D
AU  - Mitchell MD
FAU - Keelan, Jeffrey A
AU  - Keelan JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alcohol Drinking/*adverse effects
MH  - Blotting, Western
MH  - Cytochrome P-450 CYP1A1/analysis/metabolism
MH  - Cytochrome P-450 CYP1A2/analysis/metabolism
MH  - Cytochrome P-450 CYP2E1/analysis/metabolism
MH  - Female
MH  - *Gestational Age
MH  - Glucuronidase/analysis/metabolism
MH  - Glucuronosyltransferase/analysis/metabolism
MH  - Humans
MH  - *Maternal Age
MH  - Placenta/*enzymology
MH  - Pregnancy
MH  - Smoking/*adverse effects
EDAT- 2002/09/28 04:00
MHDA- 2003/03/05 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2003/03/05 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - 10.1093/humrep/17.10.2564 [doi]
PST - ppublish
SO  - Hum Reprod. 2002 Oct;17(10):2564-72. doi: 10.1093/humrep/17.10.2564.