Effects of xenoestrogen bisphenol A on uterine and pituitary weight, serum prolactin levels and immunoreactive prolactin cells in ovariectomized Wistar rats

Abstract

Considerable attention has currently been focused on bisphenol A (BPA), an environmental endocrine disrupting chemical that has oestrogenic activity. In vitro and in vivo short-term assays have shown that BPA is weakly estrogenic. In addition, the issue of species- and strain-differences in susceptibility to BPA was raised. The treatment of ovariectomized (OVX) Wistar rats with BPA at doses of 11-250 mg/kg per day, s.c., for 7 days, resulted in significant dose-dependent regrowth of uterus in uterotrophic assay. Additionally, the stimulation of anterior pituitary gland growth and induction of hyperprolactinaemia, as determined by wet organ weight and radioimmunoassay (RIA), respectively, were also dose-dependent (at 128 and 250 mg/kg per day, P < 0.05). Prolactin immunostaining of anterior pituitary glands revealed that BPA at a dose of 250 mg/kg per day increased the number of prolactin-immunopositive cells by 63% compared to OVX rats. These results demonstrate that the reproductive tract and neuroendocrine axis of Wistar rats are able to respond to BPA. Furthermore, the pituitary gland hypertrophy and hyperprolactinaemia can be mediated, at least partly, by increase in number of prolactin-immunoreactive cells. The long-term consequences of this proliferation are yet unknown but neoplasm formation is an obvious possibility.

Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.

“…They reported that BPA exhibited uterotrophic responses in 3-day uterotrophic assay using immature rats only at higher dosage (400 mg/kg/day, oral and s.c.). However, Goloubkova et al (2000) showed that the treatment of OVX Wistar rats with BPA at doses of 11-250 mg/kg resulted in significant dose-dependent uterus regrowth. We predict that the OVX rat might be more sensitive to estrogenic responses than immature rats in uterotrophic assay for BPA.…”

Effects of in Utero and Lactational Exposure to Bisphenol A on Somatic Growth and Anogenital Distance in F1 Rat Offspring.

“…BPA induced prolactin (PRL) release in vitro 4,5) . It also increased uterine and pituitary weight, the serum PRL level and the number of immunoreactive PRL cells in ovariectomized Wistar rats 6) . Reproductive toxicity of BPA has been reported in mice and rats.…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…4.2.1 Female 4.2.1.1 Rat: Goloubkova et al (2000), supported by the Brazilian National Council of Scientific and Technological Development and the National University of Rio Grande Do Sul, examined the effects of bisphenol A exposure on the uterus and pituitary of ovariectomized rats. Wistar rats (60-67 days old) were fed a standard certified rodent diet.…”