BISPHENOL A INFLUENCES OESTROGEN- AND THYROID HORMONE-REGULATED THYROID HORMONE RECEPTOR EXPRESSION IN RAT CEREBELLAR CELL CULTURE

Thyroid hormones (THs) and oestrogens are crucial in the regulation of cerebellar development. TH receptors (TRs) mediate these hormone effects and are regulated by both hormone families. We reported earlier that THs and oestradiol (E-2) determine TR levels in cerebellar cell culture. Here we demonstrate the effects of low concentrations (10(-10) M) of the endocrine disruptor (ED) bisphenol A (BPA) on the hormonal (THs, E-2) regulation of TR alpha,beta in rat cerebellar cell culture. Primary cerebellar cell cultures, glia-containing and glia-destroyed, were treated with BPA or a combination of BPA and E-2 and/or THs. Oestrogen receptor and TH receptor mRNA and protein levels were determined by real-time qPCR and Western blot techniques. The results show that BPA alone decreases, while BPA in combination with THs and/or E-2 increases TR mRNA expression. In contrast, BPA alone increased receptor protein expressions, but did not further increase them in combination with THs and/or E-2. The modulatory effects of BPA were mediated by the glia; however, the degree of changes also depended on the specific hormone ligand used. The results signify the importance of the regulatory mechanisms interposed between transcription and translation and raise the possibility that BPA could act to influence nuclear hormone receptor levels independently of ligand-receptor interaction.