论文部分内容阅读
Aim:To explore the influence and possible mechanism of xenobiotics on adrenalsteroidogenesis during fetal development.Methods:Primary human fetal adrenalcortical cells were prepared,cultured and treated with 3-methylcholanthrene,phe-nobarbital and dexamethasone.The activities of 7-ethoxyresorufin O-dealkylase,benzphetamine,aminopyrine and erythromycin N-demethylases were measuredby enzyme assays.At the same time,quantitative analysis of steroid hormonescortisol,aldosterone,testosterone and progesterone were carried out in culturalmedium by radioimmunoassays.Results:The activities of benzphetamine andaminopyrine N-demethylase were increased in the cultural fetal adrenal cells treatedwith phenobarbital(0.25-1 mmol/L)for 24h.Dexamethasone(25-100 μmol/L)alsoincreased the activity of erythromycin N-demethylase.The activity of 7-ethoxyresorufin O-dealkylase was undetected in the cells treated without andwith 3-methylcholanthrene(0.5-2μmol/L).Meanwhile,the contents of mediumcortisol,aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene.Cortisol,aldosterone and progesterone concentrations werealso slightly decreased with phenobarbital.Dexamethasone enhanced the pro-ductions of cortisol and progesterone remarkably.The trend of testosteroneconcentration was uncertain after 3-methylcholanthrene,phenobarbital or dexam-ethasone treatment.Conclusion:3-Methylcholanthrene,phenobarbital or dex-amethasone could interfere with the synthesis of cortisol,aldosterone and proges-terone in primary human fetal adrenal cortical cells,which likely act throughxenobiotic metabolizing-related cytochrome P450 isoform activation.
Aim: To explore the influence and possible mechanism of xenobiotics on adrenalsteroidogenesis during fetal development. Methods: Primary human fetal adrenalcortical cells were prepared, cultured and treated with 3-methylcholanthrene, phe-nobarbital 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 hormonescortisol, aldosterone, testosterone and progesterone were carried out in cultural media 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 24h .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 andwith 3-methylcholanthrene (0.5-2 μmol / L). However, the contents of medium cortisol, aldoste rone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the pro-ductions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexam -ethasone treatment.Conclusion: 3-Methylcholanthrene, phenobarbital or dex-amethasone could interfere with the synthesis of cortisol, aldosterone and proges-terone in primary human fetal adrenal cortical cells, which likely act throughxenobiotic metabolizing-related cytochrome P450 isoform activation.