Exposure of newborn male and female rats to environmental estrogens: Delayed and sustained hyperprolactinemia and alterations in estrogen receptor expression

Environmental estrogens (xenoestrogens) are synthetic compounds that are ab undant in the environment and mimic natural estrogens. The estrogenicity of two such compounds, bisphenol A (BPA) and octylphenol (OP), during develop ment of the neuroendocrine system was investigated. The objective was to co mpare the effects of neonatal exposure to BPA, OF, and diethylstilbestrol ( DES), a potent synthetic estrogen, on prepubertal serum PRL levels and estr ogen receptor (ER) expression in the anterior pituitary and medial basal hy pothalamus. Receptor expression in the uterus and prostate, two peripheral estrogen-responsive tissues, was also examined. Newborn male and female Fis cher 344 rats were sc injected on days 1-5 after birth with corn oil (contr ol), BPA and OP (100 or 500 mug/day), or DES (5 mug/day). Rats were bled on days 15, 20, and 25 and on the day of death (day 30), and serum PRL was an alyzed by RIA. Relative expressions of ER alpha and ER beta were determined by RT-PCR. BPA and OP induced delayed, but progressive, increases in serum PRL levels, up to 3-fold above control levels, in both males and females. The low dose of either compound was equally or more effective as the high d ose in eliciting and sustaining elevated serum PRL levels, namely hyperprol actinemia. In contrast, the DES treatment resulted in a transient rise in s erum PRL levels. BPA, OF, and, to a lesser extent, DES increased the expres sion of both ER alpha and ER beta in the anterior pituitary of males, but n ot females, whereas the hypothalamic ERs were less responsive to these comp ounds. DES treatment caused downregulation of ER alpha expression in the ut erus and up-regulation of ER beta in the prostate, whereas BPA or OP was wi thout effect. In conclusion, exposure of newborn rats of either sex to envi ronmental estrogens results in delayed and sustained hyperprolactinemia and differential alterations in ER expression in the hypothalamus and pituitar y. DES appears to target the lower reproductive tract more effectively than the neuroendocrine system.