Acta Pharmacologica Sinica 2008 February; 29 (2): 231-238; doi: 10.1111/j.1745-7254.2008.00738.x

 
Original Article
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Changes of multiple biotransformation phase I and phase II enzyme activities in human fetal adrenals during fetal development1
 

Hui WANG2, Jie PING2, Ren-xiu PENG2, Jiang YUE2, Xue-yan XIA2, Qi-xiong LI2, Rui KONG2, Jun-yan HONG2,3

2Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; 3School of Public Health, Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, N J 08854, USA

 

Aim: 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 a glutathione S-transferase (GST), pGST, and µGST in adrenals were 0.5, 4.4, and 8.3-fold of those in the livers, respectively, and the activity of adrenal pGST 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.


Conclusion:
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.

 

Keywords: human fetus; adrenal; cytochrome P450; glutathione S-transferase; uridine diphosphoglucuronyl transferase

 
1 Project supported by the National Natural Science Foundation of China (No 30672566).

4 Correspondence to Prof Hui WANG.
Phn 86-27-6875-8665.
Fax 86-27-8733-1670.
E-mail clbwhcbd@yahoo.com
Received 2007-07-07     Accepted 2007-09-12

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