Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human...

Sex steroid hormones exert important influences on neuroendocrine and behavioural brain function. As neuroactive steroids they are able to modify neuronal excitability. Unbalanced synthesis may thus be implicated in pathophysiological conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial role in catalyzing the final steps of androgen and estrogen biosynthesis. The hippocampus appears to be a major target area of neurosteroidal action. The expression of 17beta-HSD isozymes has not yet been studied in human hippocampus. Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in hippocampal tissue specimens obtained at neurosurgery from 42 patients with pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000 fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3 mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4 concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus showed no significant differences between men and women and there were no significant differences in expression levels of these enzymes between patients with Ammon's horn sclerosis (AHS) and those with histopathologically normal hippocampus associated with extrahippocampal lesions. No significant correlation could be detected between duration of epilepsy, individual seizure frequency and expression levels of 17beta-HSDs. In conclusion, the present study is the first to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the human hippocampus also, our data provide further evidence for the existence of sex steroid formation and metabolism in this specific brain area.