Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells.
OBJECTIVE
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 micromol/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 micromol/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.


CONCLUSIONS
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.
Wang
Hui
H
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. clbwhcbd@yahoo.com
Huang
Min
M
Peng
Ren-Xiu
RX
Le
Jiang
J
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D001589:Benzphetamine / Q000378:metabolism; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005333:Fetus; D006801:Humans; D008748:Methylcholanthrene / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D011282:Pregnenediones / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism
D011282:Pregnenediones; D015262:Xenobiotics; D001589:Benzphetamine; D008748:Methylcholanthrene; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital