Influence of menstrual cycle on cyp1a2 in vivo activity determined with caffeine phenotyping
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1
University of Thessaly, Laboratory of Pharmacology, Greece
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2
University of Thessaly, Laboratory of Pathology, Greece
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3
University of Thessaly, Obstetrics & Gynecology Clinic, Greece
Introduction. Caffeine is commonly used as a probe drug for the simultaneous assessment of the phenotypes of various drug-metabolizing enzymes including CYP1A2, CYP2A6, XO and NAT-2. Human CYP1A2 is responsible for the metabolism of endogenous compounds such as 17β-estradiol and it is involved in the metabolism of many clinically used drugs as well as the activation of pro-carcinogenic compounds. The activity of CYP1A2 has been shown to be decreased by female sex hormones, during pregnancy or treatment with oral contraceptives. Recently, we have shown that CYP1A2 activity declines during menopause. An investigation has now been made into whether the changes in sex steroid levels that occur during normal menstrual cycling also affect the rate of caffeine metabolism.
Methods and results. CYP1A2 activity was monitored in 43 (23 non-smokers, NS and 20 smokers, S) healthy, regularly menstruating, age matched (NS: 30.67±1.67y, S: 29.00±3.60; p>0.05) women using caffeine as a metabolic probe. Blood and urine samples were collected during early-, late- follicular and luteal phases (EFP, LFP and LP, respectively). Oestradiol, progesterone, LH and FSH serum levels were determined in all three phases. Caffeine metabolic ratios (CMRs) were calculated using HPLC in spot urine samples analysed 6h after 200mg caffeine consumption, following a 30h methylxanthine-free diet. Comparisons of mean (±SEM) CMRs during the three phases revealed that CYP1A2 activity was significantly reduced in the late- compared to early- follicular and luteal phases in both NS (EFP: 3.1±0.23, LFP: 2.65±0.15, LP: 2.98±0.20; p<0.05) and S (EFP: 5.92±1.10, LFP: 4.24±0.56, LP: 4.88±0.50; p<0.05) subjects. The reduction in CYP1A2 activity was inversely related to levels of oestradiol.
Conclusion. The present study demonstrates reduced CMRs in the late follicular phase of the normal menstrual cycle suggesting that normal fluctuations in sex steroid levels during the phases of normal menstrual cycle may be associated with variation with CYP1A2 activity.
Keywords:
CYP1A2,
Caffeine,
HPLC
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Oral
Topic:
Xenobiotic metabolism
Citation:
Tsiokou
V,
Begas
E,
Kouvaras
E,
Messinis
I and
Asprodini
E
(2010). Influence of menstrual cycle on cyp1a2 in vivo activity determined with caffeine phenotyping.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00209
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Received:
07 Mar 2011;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Eftihia Asprodini, University of Thessaly, Laboratory of Pharmacology, Thessaly, Greece, easpro@med.uth.gr