Exposure of Newborn Male and Female Rats to Environmental Estrogens: Delayed and Sustained Hyperprolactinemia and Alterations in Estrogen Receptor Expression**This work was supported by NIH Grants ES-09555, ES-10154, and CA-80920; March of Dimes Grant 6-FY98–0159; and a grant from the Pardee Foundation. Preliminary results of this investigation were presented at the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, June 2000.

Abstract

Environmental estrogens (xenoestrogens) are synthetic compounds that are abundant in the environment and mimic natural estrogens. The estrogenicity of two such compounds, bisphenol A (BPA) and octylphenol (OP), during development of the neuroendocrine system was investigated. The objective was to compare the effects of neonatal exposure to BPA, OP, and diethylstilbestrol (DES), a potent synthetic estrogen, on prepubertal serum PRL levels and estrogen receptor (ER) expression in the anterior pituitary and medial basal hypothalamus. Receptor expression in the uterus and prostate, two peripheral estrogen-responsive tissues, was also examined. Newborn male and female Fischer 344 rats were sc injected on days 1-5 after birth with corn oil (control), BPA and OP (100 or 500 g/day), or DES (5 g/day). Rats were bled on days 15, 20, and 25 and on the day of death (day 30), and serum PRL was analyzed by RIA. Relative expressions of ER␣ and ER␤ 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 dose in eliciting and sustaining elevated serum PRL levels, namely hyperprolactinemia. In contrast, the DES treatment resulted in a transient rise in serum PRL levels. BPA, OP, and, to a lesser extent, DES increased the expression of both ER␣ and ER␤ in the anterior pituitary of males, but not females, whereas the hypothalamic ERs were less responsive to these compounds. DES treatment caused downregulation of ER␣ expression in the uterus and up-regulation of ER␤ in the prostate, whereas BPA or OP was without effect. In conclusion, exposure of newborn rats of either sex to environmental estrogens results in delayed and sustained hyperprolactinemia and differential alterations in ER expression in the hypothalamus and pituitary. DES appears to target the lower reproductive tract more effectively than the neuroendocrine system. (Endocrinology 141: [4512][4513][4514][4515][4516][4517] 2000) E NVIRONMENTAL estrogens (xenoestrogens) are a diverse group of synthetic compounds that are abundant in the environment and mimic the action of estrogens. Two such compounds, bisphenol A (BPA) and octylphenol (OP), were the focus of this investigation (Fig. 1). BPA is composed of two unsaturated phenolic rings that resemble diethylstilbestrol (DES). BPA is a monomer of polycarbonate plastics and a constituent of epoxy and polystyrene resins used in the food packaging industry and dentistry (1, 2). The polymer bonds can hydrolyze at high temperature and release BPA. Detectable amounts of BPA were found in food cans (3), microwaved pizzas (4), and human saliva after treatment with dental sealants (5). OP, comprised of a single phenolic ring (Fig. 1), is a constituent of alkylphenol polyethoxylates that are used as surfactants in detergents, paints, and herbicides. Alkylphenols are degraded in treatment plants to form stable products, OP and nonylphenol, whic...

Maternal Exposure to Isobutyl-Paraben Impairs Social Recognition in Adult Female Rats

“…Similarly, previous works have shown that ER expression in animals treated with other estrogenic compounds is significantly lower than that in control animals [20,35]. Interestingly, ER plays a role in mediating social recognition in female mice, as ERα and ERβ knockout mice have specifically impaired social recognition [6].…”

The Endocrine Disrupters Butyl Benzyl Phthalate and Bisphenol A Increase the Expression of Progesterone Receptor Messenger Ribonucleic Acid in the Preoptic Area of Adult Ovariectomized Rats

“…A number of studies have been undertaken in order to check whether these chemicals alter the organizational effect of endogenous gonadal steroid hormones during the development of reproductive organs [1, 2, 3, 4, 5, 6, 7]. Most of these studies suggest that BBP and BPA exposure during differentiating and developmental stages exert irreversible effects on the reproductive organs as well as on the hypothalamic structures controlling reproductive functions.…”

NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

“…In the ovary, both nuclear estrogen receptors [ 82 ] are known to be regulators of granulosa cell differentiation, follicle and oocyte growth, and ovulation. Several papers have already proposed roles for each of these receptors in ovarian physiology [ 83 , 84 , 85 ], with ERβ playing an important role in the follicle maturation process and ovulation [ 86 ].…”