Abstract
Aim:
To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development.
Methods:
Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3-methylcholanthrene, phenobarbital and dexamethasone. The activities of 7-ethoxyresorufin O-dealkylase, benzphetamine, aminopyrine and erythromycin N-demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays.
Results:
The activities of benzphetamine and aminopyrine N-demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25-1 mmol/L) for 24 h. Dexamethasone (25-100 μmol/L) also increased the activity of erythromycin N-demethylase. The activity of 7-ethoxyresorufin O-dealkylase was undetected in the cells treated without and with 3-methylcholanthrene (0.5–2 μmol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexamethasone treatment.
Conclusion:
3-Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing-related cytochrome P450 isoform activation.
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Project supported by the grants from the Family Planning Commission of Hubei, China (2003).
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Wang, H., Huang, M., Peng, Rx. et al. Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells. Acta Pharmacol Sin 27, 1093–1096 (2006). https://doi.org/10.1111/j.1745-7254.2006.00358.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00358.x
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