Stimulatory effect of cigarette smoking on the 15α-hydroxylation of estradiol by human term placenta
Autor: | George H Lambert, Bao Ting Zhu, Yu-Ling Lai, David C. Spink, Paul E. Thomas, May Xiaoxin Cai, Angela C. Ranzini, Christine M. Busch, Mirza M. Hussain, Allan H. Conney |
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Rok vydání: | 2002 |
Předmět: |
Adult
medicine.medical_specialty animal structures medicine.drug_class Placenta Metabolite Estrone Hydroxylation Nicotine chemistry.chemical_compound Pregnancy Microsomes Internal medicine medicine Humans Pharmacology (medical) Pharmacology Estradiol Smoking Estrogens Catechol Placentation medicine.anatomical_structure Endocrinology chemistry Estrogen Toxicity Microsome Female NADP medicine.drug |
Zdroj: | Clinical Pharmacology & Therapeutics. 71:311-324 |
ISSN: | 0009-9236 |
DOI: | 10.1067/mcp.2002.122500 |
Popis: | Objective Our objective was to characterize the oxidative metabolism of estradiol by human term placenta and its modulation by cigarette smoking. Methods Placental microsomes were prepared from term placentas obtained from 13 cigarette smokers (20 to 30 cigarettes per day until the time of delivery) and 13 control subjects who were nonsmokers. Estrogen metabolism was studied by incubation of 250 nmol/L [3H]estradiol with placental microsomes and NADPH, and the estrogen metabolites were determined by HPLC and gas chromatography–mass spectrometry. Results 2-Hydroxyestradiol was the major hydroxyestrogen detected, followed by 6α-hydroxyestradiol. Small amounts of several other hydroxyestrogen metabolites (4-hydroxyestradiol, 6β-hydroxyestradiol, 7α-hydroxyestradiol, and 16α-hydroxyestradiol) were also detected. Large amounts of estrone plus small amounts of 2-hydroxyestrone and unidentified nonpolar metabolites were formed. Cigarette smoking stimulated the placental hydroxylation of benzo[a]pyrene by about 16-fold. Cigarette smoking had little or no effect on the overall rate of placental estradiol metabolism or on the formation of estrone, 2-hydroxyestradiol, 2-hydroxyestrone, or 16α-hydroxyestradiol. However, placental formation of 4-hydroxyestradiol and 7α-hydroxyestradiol was increased 38% (P = .08) and 150% (P = .05), respectively, in cigarette smokers. The formation of 6α-hydroxyestradiol was decreased 33% (P = .04). Metabolic formation of 15α-hydroxyestradiol was observed during incubations of estradiol with placental microsomes from 11 of the 13 cigarette smokers, but this metabolite was not detected during incubations with placental microsomes from any of the 13 nonsmokers. Analysis of data from all 26 placentas showed that the 15α-hydroxylation of estradiol was highly correlated with benzo[a]pyrene hydroxylation (r = 0.93; P < .001). Conclusions Many hydroxylated estradiol metabolites were formed by placental microsomes from cigarette smokers and nonsmokers. 15α-Hydroxylation of estradiol was markedly stimulated in the placentas of cigarette smokers. Clinical Pharmacology & Therapeutics (2002) 71, 311–324; doi: 10.1067/mcp.2002.122500 |
Databáze: | OpenAIRE |
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