Gene expression of cytochrome P450 1B1 and 2D6 in leukocytes in human pregnancy.
We investigated the influence of human pregnancy on gene expression of two cytochrome P450 enzymes in white blood cells. Cytochrome P450 1B1 (CYP1B1) catalyses oestradiol 4-hydroxylation, and may participate in the endocrine regulation of oestrogens. Cytochrome P450 2D6 (CYP2D6) metabolises many commonly used drugs, and previous studies have suggested that it is induced during pregnancy. CYP1B1 and CYP2D6 were therefore considered to be of interest in human pregnancy. As it is not ethically possible to take liver biopsies from healthy mothers during pregnancy, easily accessible cells that express the genes were used as a surrogate tissue. White blood cells were collected from eighteen pregnant women, and were used to measure CYP1B1 and CYP2D6 ribonucleic acid (RNA). The analysis was repeated after pregnancy, the women, thus, serving as their own controls. Real-time reverse transcriptase - polymerase chain reaction methods were used with 18S ribosomal RNA as an internal control. A slight, but not significant, increase in gene activity of CYP1B1 was detected during pregnancy. Expression of CYP2D6 in blood was extremely low, and induction of CYP2D6 during pregnancy could not be confirmed. In conclusion, gene expression of CYP1B1 and CYP2D6 in leukocytes was not significantly up-regulated in the third trimester of pregnancy, but a trend indicating an altered metabolism during pregnancy was detected.
Lind
Anna-Britta
AB
Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Wadelius
Mia
M
Darj
Elisabeth
E
Finnström
Niklas
N
Lundgren
Stefan
S
Rane
Anders
A
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D011247:Pregnancy / Q000097:blood / Q000378:metabolism*; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012337:RNA, Ribosomal, 18S; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D019389:Cytochrome P-450 CYP2D6