Changes of multiple biotransformation phase I and phase II enzyme activities in human fetal adrenals during fetal development.
OBJECTIVE
Fetal adrenal, which synthesizes steroid hormones, is critical to fetal growth and development. Our recent research showed that some xenobiotics could interfere with steroidogenesis and induce intrauterine growth retardation in rats. The study on the characteristics of biotransformation enzymes in fetal adrenals still seems to be important with respect to possible significance in xenobiotic-induced fetal development toxicity. In this study, the activities of several important xenobiotic-related phase I and phase II enzymes in human fetal adrenals were examined and compared with those in fetal livers.


METHODS
The activity and mRNA expression were determined by enzymatic analysis and RT-PCR.


RESULTS
The levels of cytochrome (CYP)2A6, CYP2E1, and CYP3A7 isozymes in fetal adrenals were 82%, 92%, and 33% of those in fetal livers, respectively. There was a good positive correlation between adrenal CYP2A6 activity and gestational time. The values of alpha glutathione S-transferase (GST), pi-GST, and microGST in adrenals were 0.5, 4.4, and 8.3-fold of those in the livers, respectively, and the activity of adrenal pi-GST was negatively correlated with gestational time. The uridine diphosphoglucuronyl transferase activities, which were measured using p-hydroxy-biphenyl and 7-hydroxy-4-methylcoumarin as substrates, were 9% and 3%, respectively, of those in the fetal livers.


CONCLUSIONS
Our investigation suggested that adrenal could be an important xenobiotic-metabolizing organ in fetal development and may play a potential role in xenobiotic-induced fetal development toxicity.
Wang
Hui
H
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. clbwhcbd@yahoo.com
Ping
Jie
J
Peng
Ren-xiu
RX
Yue
Jiang
J
Xia
Xue-yan
XY
Li
Qi-xiong
QX
Kong
Rui
R
Hong
Jun-yan
JY
D000311:Adrenal Glands / Q000196:embryology* / Q000201:enzymology*; D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005865:Gestational Age; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D011247:Pregnancy; D013347:Subcellular Fractions / Q000201:enzymology; D015262:Xenobiotics / Q000378:metabolism
D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase