Effects of Polychlorinated Biphenyls on Estrogen Receptor-[Beta] Expression in the Anteroventral Periventricular Nucleus
Salama, Jacklyn, Chakraborty, Tandra R., Ng, Laurie, Gore, Andrea C., Environmental Health Perspectives
Polychlorinated biphenyls (PCBs) can disrupt the reproductive axis, particularly when the exposure occurs during the vulnerable developmental periods. Some effects of environmental endocrine disruptors such as PCBs may be exerted through binding to estrogen receptors (ERs). In this study we examined the endocrine-disrupting effects of Aroclor 1221 (a commercial PCB mixture), focusing on its actions on the ER-[beta], which has been implicated in mediating effects of endocrine-disrupting chemicals. A low, ecologically relevant dose of Aroclor 1221 or vehicle (ethanol) was administered three times each to rat dams, on gestational day 16 and on postpartum days 1 and 4, a developmental period during which steroid hormones have permanent effects on adult brain structure and function. Effects on ER-[beta] cell number in the anteroventral periventricular nucleus (AVPV) were quantified; this sexually dimorphic nucleus of the brain is essential to female reproductive function. For comparison, we quantified ER-[beta] cell number in another hypothalamic region, the supraoptic nucleus (SON). Using a stereologic approach, we found that Aroclor 1221 caused a highly significant down-regulation of the number of ER-[beta]-expressing cells in the AVPV, but had no effect in the SON. Thus, PCB exposure has consequences for neural ER expression, and these findings have implications for wildlife and humans that have been exposed to environmental estrogens, particularly during the susceptible periods of early development. Key words: anteroventral periventricular nucleus, Aroclor 1221, estrogen receptor, hypothalamus, PCB, puberty, supraoptic nucleus.
Endocrine-disrupting chemicals (EDCs) are substances found in the environment that interfere with the endocrine system by acting as agonists or antagonists to hormone receptors. Polychlorinated biphenyls (PCBs) can act as EDCs; depending upon their structures, they can act at estrogen receptors (ERs), androgen receptors, or thyroid hormone receptors (Conner et al. 1997; Jansen et al. 1993; Kester et al. 2000; Sager 1983; Zoeller 2002) and interfere with the enzymes involved in steroid hormone biosynthesis and metabolism (Hany et al. 1999; Kester et al. 2000). Although the production of PCBs has been outlawed in the United States since 1979, these chemicals persist in the air, water, and soil and biomagnify within the food chain (Evans et al. 1991; Safe et al. 1987; Tilson et al. 1998).
The brains of developing male rodents are naturally exposed to sex steroid hormones (testosterone and its metabolite estradiol) that are synthesized in the developing male testis (Barraclough 1961; Doecke et al. 1978; Ramaley 1979). The ovary of female rodents, by contrast, is essentially quiescent, resulting in relatively low exposure of the developing female brain to gonadal hormones (Barradough 1961; Doecke et al. 1978; Ramaley 1979). These normal sex differences in perinatal steroid hormone exposure result in adulthood in normal male- and female-typical neuroendocrine function (e.g., secretion of gonadotropins), reproductive behavior, and other nonreproductive functions (Davis et al. 1996; Laessig et al. 1999; McEwen and Alves 1999; Simerly 2002). Therefore, exposure of the female brain to exogenous steroids, including estrogenic EDCs, during critically sensitive stages of development can have masculinizing or defeminizing effects (Atanassova et al. 2000; Barraclough 1961; Chung and Clemens 1999; Conner et al. 1997; Cooper and Kavlock 1997; Newland and Paletz 2000). For example, prenatal treatment of female rodents and other species with PCBs and other EDCs has been shown to alter the timing of puberty (Faqi et al. 1998; Lundkvist 1990), accelerate reproductive aging (Cooper and Kavlock 1997; Gellert 1978), affect gonadotropin release (Jansen et al. 1993; Khan and Thomas 1997), and interfere with sexual behavior (Chung and Clemens 1999).
In the present study, we used an environmentally relevant dose (Bush et al. …