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Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Casilla de Correo 242, 3000 Santa Fe, Argentina

(Requests for offprints should be addressed to J G Ramos; Email: gramos{at}fbcb.unl.edu.ar)

The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor (ER) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0.05 mg/kg) or diethylstilbestrol (DES, 0.02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ER transcripts containing alternative 5'-untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ER promoters was determined by bisulfited DNA restriction analysis and ER protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ER mRNA levels, mediated by the decreased expression of ER-O and ER-OT variants. In contrast, the low dose of BPA augmented total ER mRNA by increasing the expression of the ER-E1 variant. In PND21, both BPA doses increased total ER mRNA by means of the augmented expression of ER-O and ER-OT variants. In PND21, the methylation status of the ER promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ER protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ER transcript variants and protein in a dose-dependent manner.

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