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1295514 
Journal Article 
Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model 
Gustavsen, MW; von Krogh, K; Taubøll, E; Zimmer, KE; Dahl, E; Olsaker, I; Ropstad, E; Verhaegen, S 
2009 
Yes 
Acta Neurologica Scandinavica. Supplementum
ISSN: 0065-1427
EISSN: 1600-5449 
189 
14-21 
English 
19566492 
OBJECTIVES: To better understand the interaction of antiepileptic drugs and production of sex hormones, possible effects of valproate (VPA), levetiracetam (LEV) and carbamazepine (CBZ) on steroidogenesis were investigated in the human adrenal carcinoma cell line H295R.

MATERIALS AND METHODS: H295R cells were exposed to different concentrations of VPA, LEV or CBZ for 48 h. Sex hormone concentrations and mRNA expression levels were analyzed via radioimmunoassay and quantitative real time (RT)-PCR, respectively.

RESULTS: In VPA-exposed cells estradiol levels decreased in a dose-dependent manner, while testosterone and progesterone levels were unaffected. Expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), steroidogenic acute regulatory protein (StAR), CYP11a, CYP17, CYP21, 3betaHSD2, 17betaHSD1 was downregulated and expression of CYP11beta2 was upregulated. No effect on sex hormone production was observed under influence of LEV or CBZ. Expression of StAR, CYP17, CYP19 and 3betaHSD2 was downregulated in LEV-exposed cells, and expression of HMGR, CYP11beta2 and CYP17 was downregulated in CBZ-exposed cells.

CONCLUSIONS: VPA exposure resulted in a decrease in estradiol levels and a general downregulation of expression of genes encoding for enzymes early in steroidogenesis. No consistent changes were seen with LEV or CBZ exposure.