Expression and cyclic variability of CYP3A4 and CYP3A7 isoforms in human endometrium and cervix during the menstrual cycle.
CYP3A4, a cytochrome p450 (p450) isoform metabolizes estrogens, whereas CYP3A7, a fetal liver p450 isoform, is involved in estriol biosynthesis. The goal of this study was to evaluate expression of these enzymes in human uterine tissue during the proliferative and secretory phases of the menstrual cycle. Endometrium and cervix specimens were collected from women undergoing hysterectomy (n = 36). Total mRNA was extracted, quantified, and reverse-transcription polymerase chain reaction (RT-PCR) was carried out using consensus primers for CYP3A. The 453 base pairs PCR product was hybridized with specific internal oligonucleotide probes for CYP3A4 or CYP3A7 end labeled with (32)P gamma-ATP. The relative intensity of hybridization was determined by autoradiography. Expression of CYP3A7 in endometrium was significantly greater (approximately 10-fold) in the proliferative phase compared with the secretory phase (p < 0.05). CYP3A4 expression was comparable between the two phases. Expression of both enzymes was minimal in the cervix. Fluorescence in situ hybridization of paraffinized sections indicated localized expression of CYP3A enzymes in the glandular epithelium as well as the stroma. Comparison of relative fluorescence intensity indicated differential expression of CYP3A7 in various phases of the menstrual cycle. These results suggest that CYP3A expression in the endometrium of premenopausal women may vary depending on the menstrual cycle phase.
Sarkar
Mohamadi A
MA
Virginia Commonwealth University School of Pharmacy, Medical College of Virginia Campus, Richmond 23298-0533, Virginia. masarkar@vcu.edu
Vadlamuri
Vijay
V
Ghosh
Shobha
S
Glover
Douglas D
DD
D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D002584:Cervix Uteri / Q000201:enzymology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004717:Endometrium / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008597:Menstrual Cycle / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human