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.

Maternal fructose consumption alters messenger RNA expression of hippocampal StAR, PBR, P450(11β), 11β-HSD, and 17β-HSD in rat offspring

“…We have studied the regulatory mechanism of hippocampal neurosteroid synthesis. We previously reported that tributyltin, an environmental pollutant, and 9-cis-retinoic acid regulate hippocampal neurosteroid synthesis [14,15]. We also clarified that social isolation stress stimulates hippocampal estradiol synthesis [13].…”

“…Comparative threshold cycle values were used to determine relative mRNA expression levels, as described previously [20]. Real-time PCR results were normalized by GAPDH expression levels [14,15]. Polymerase chain reaction primers were listed in a previous report [21].…”

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

“…In contrast, TBT mitigated OVX-induced weight gain and adiposity and reduced serum insulin levels. Classically, TBT is thought of as an aromatase inhibitor [35]; however, evidence also suggests that TBT can enhance estradiol synthesis [43, 44]. A potential mechanism by which TBT could mitigate the effects of OVX could be through stimulating estrogen production by extra-gonadal tissues [45].…”

Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects

“…Tributyltin induced an increase in the mRNA content of P450(17a) and P450arom in rat hippocampal slices. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes (Munetsuna et al, 2014).…”