The Environmental Estrogen Bisphenol A Stimulates Prolactin Release in Vitro and in Vivo*

Abstract

Environmental estrogens (xenoestrogens) are a diverse group of chemicals that mimic estrogenic actions. Bisphenol A (BPA), a monomer of plastics used in many consumer products, has estrogenic activity in vitro. The pituitary lactotroph is a well established estrogen-responsive cell. The overall objective was to examine the effects of BPA on PRL release and explore its mechanism of action. The specific aims were to: 1) compare the potency of estradiol and BPA in stimulating PRL gene expression and release in vitro; 2) determine whether BPA increases PRL release in vivo; 3) examine if the in vivo estrogenic effects are mediated by PRL regulating factor from the posterior pituitary; and 4) examine if BPA regulates transcription through the estrogen response element (ERE). BPA increased PRL gene expression, release, and cell proliferation in anterior pituitary cells albeit at a 1000- to 5000-fold lower potency than estradiol. On the other hand, BPA had similar efficacy to estradiol in inducing hyperprolactinemia in estrogen-sensitive Fischer 344 (F344) rats; Sprague Dawley (SD) rats did not respond to BPA. Posterior pituitary cells from estradiol- or BPA-treated F344 rats strongly increased PRL gene expression upon coculture with GH3 cells stably transfected with a reporter gene. Similar to estradiol, BPA induced ERE activation in transiently transfected anterior and posterior pituitary cells. We conclude that: a) BPA mimics estradiol in inducing hyperprolactinemia in genetically predisposed rats; b) the in vivo action of estradiol and BPA in F344 rats is mediated, at least in part, by increasing PRL regulating factor activity in the posterior pituitary; c) BPA appears to regulate transcription through an ERE, suggesting that it binds to estrogen receptors in both the anterior and posterior pituitaries. The possibility that BPA and other xenoestrogens have adverse effects on the neuroendocrine axis in susceptible human subpopulations is discussed.

Developing hypothalamic dopaminergic neurones as potential targets for environmental estrogens

“…While the sensitivity of response may change with the age of the developing cultures, we have observed effects at 10 -14 M for E 2 and 10 -11 M for OP. This is in keeping with other findings that in vitro the xenoestrogens are several orders of magnitude less potent than E 2 (White et al 1994, Steinmetz et al 1997, although the sensitivity of the cultured cells appears extremely high. Significant effects of low dose E 2 and BPA have also been reported on prolactin release from cultured anterior pituitary cells obtained from adult rats of the estrogensensitive Fisher rat strain (Steinmetz et al 1997).…”

“…This is in keeping with other findings that in vitro the xenoestrogens are several orders of magnitude less potent than E 2 (White et al 1994, Steinmetz et al 1997, although the sensitivity of the cultured cells appears extremely high. Significant effects of low dose E 2 and BPA have also been reported on prolactin release from cultured anterior pituitary cells obtained from adult rats of the estrogensensitive Fisher rat strain (Steinmetz et al 1997). Whilst prolactin release elicited by the lowest dose of BPA tested (10 -8 M) was not much greater than control, the response to the Table 1 Contribution of glial cells to [ 3 H]DA uptake.…”

“…While this link is not proven, many studies now document the ability of these chemicals to interfere with the actions of steroid hormones in wildlife (Colborn & Clement 1992, Colborn et al 1993, Guillette et al 1996 and in experimental animals (Malby et al 1992, White et al 1994, Steinmetz et al 1997, vom Saal et al 1998. Increasingly attention is focused on early life stages when steroid hormones play a crucial role in the development of many tissues and organs which undergo distinct periods of enhanced developmental sensitivity.…”

Modulation of the Expression of Bloom Helicase by Estrogenic Agents

“…11,20) If ER participates in the regulation of BLM expression, BPA is also expected to affect BLM expression. Figure 2A shows that 10…”

Cross-talk between endocrine-disrupting chemicals and cytokine signaling through estrogen receptors

“…It has been actually shown that the in vivo effects of EDCs such as Bisphenol A mimic those of 17β-estradiol (E2), including the vaginal cornification (8), growth and differentiation of the mammary gland (9), a decreased cholesterol level in serum (10), an increased prolactin level (11), and an increased c-fos mRNA level in the uterus (8), suggesting that EDCs have enough potential to alter reproductive function and endocrine system in vivo. However, we do not know whether the EDCs can modify other cellular signaling such as growth factors or cytokines.…”