title: Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.
abstract: Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.
authors.affiliation: Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University , Higashihiroshima , Japan .
authors.forename: Eiji
authors.initials: E
authors.lastname: Munetsuna
authors.forename: Minoru
authors.initials: M
authors.lastname: Hattori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D065693:Cytochrome P-450 Enzyme Inducers / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000032:analysis / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D047488:Retinoid X Receptors / Q000819:agonists / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques; D014220:Trialkyltin Compounds / Q000633:toxicity*
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D004785:Environmental Pollutants; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D014220:Trialkyltin Compounds; D004958:Estradiol; C011559:tributyltin; D001141:Aromatase; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase
keywords: Estradiol; hippocampus; neurosteroid; tributyltin