Chun T Y, Gorski J
Department of Biochemistry, University of Wisconsin, Madison, Wisconsin, 53706, USA.
Toxicol Appl Pharmacol. 2000 Feb 1;162(3):161-5. doi: 10.1006/taap.1999.8840.
PR1 cells are a prolactin (PRL)-secreting cell line derived from pituitary lactotroph tumors found in 17beta-estradiol (E(2))-treated female Fischer 344 rats. Recently, we reported that as little as 0. 01 pM E(2) could induce half-maximal cell proliferation, whereas the antiestrogen ICI 182,780 (ICI) inhibited proliferation. Interestingly, the cell proliferation response is 1000-fold more sensitive to E(2) than the PRL response (induction of prolactin protein synthesis), suggesting that there is a distinction between cell proliferation and the PRL response in PR1 cells. Bisphenol A (BPA) is a monomer of plastics and epoxy resins that is widely used in dentistry and the food packaging industry. Although it has low estrogenic activity in somatolactotrophs and breast cancer cell lines, its presence in the environment and its long biological half-life have raised concerns about potential effects in humans. We analyzed the effect of BPA and compared its activity with E(2) in the PR1 cell line. PR1 cells show half-maximal proliferation upon treatment with 10 nM BPA, which is 10,000- to 100,000-fold less active than E(2). BPA-induced PR1 cell proliferation is decreased by the pure antiestrogen ICI, suggesting that BPA-induced PR1 cell proliferation is mediated by the estrogen receptor (ER). The decreased affinity of BPA for the ER is illustrated by the fact that 1 nM of ICI inhibited 100 nM BPA-induced cell proliferation, whereas 100 nM ICI was required to block 1 nM E(2)-induced cell proliferation. The PRL response to BPA required 1000 nM BPA to match the PRL secretion induced by 0.01 nM E(2). A competitive binding assay showed that the K(i) of BPA for the ER in PR1 cells is approximately 30-60 nM, which is 1000- to 2000-fold lower than that of E(2). Our study suggests the PR1 cell line can be used as an in vitro assay system for analyzing the effects of weak estrogens on ER-mediated responses and the activities of various estrogenic compounds present in small amounts in the environment.
PR1细胞是一种分泌催乳素（PRL）的细胞系，源自17β-雌二醇（E₂）处理的雌性Fischer 344大鼠的垂体催乳细胞肿瘤。最近，我们报道低至0.01 pM的E₂就能诱导半数最大细胞增殖，而抗雌激素ICI 182,780（ICI）可抑制增殖。有趣的是，细胞增殖反应对E₂的敏感性比对PRL反应（催乳素蛋白合成的诱导）高1000倍，这表明PR1细胞中细胞增殖和PRL反应之间存在差异。双酚A（BPA）是塑料和环氧树脂的单体，广泛应用于牙科和食品包装行业。尽管它在生长催乳细胞和乳腺癌细胞系中具有低雌激素活性，但其在环境中的存在及其长生物半衰期引发了对其对人类潜在影响的担忧。我们分析了BPA的作用，并将其活性与E₂在PR1细胞系中的活性进行了比较。PR1细胞在10 nM BPA处理后出现半数最大增殖，其活性比E₂低10000至100000倍。纯抗雌激素ICI可降低BPA诱导的PR1细胞增殖，这表明BPA诱导的PR1细胞增殖是由雌激素受体（ER）介导的。1 nM的ICI可抑制100 nM BPA诱导的细胞增殖，而阻断1 nM E₂诱导的细胞增殖则需要100 nM ICI，这一事实说明了BPA与ER的亲和力降低。对BPA的PRL反应需要1000 nM BPA才能与0.01 nM E₂诱导的PRL分泌相匹配。竞争结合试验表明，BPA在PR1细胞中对ER的抑制常数（Kᵢ）约为30 - 60 nM，比E₂低1000至2000倍。我们的研究表明，PR1细胞系可作为一种体外分析系统，用于分析弱雌激素对ER介导反应的影响以及环境中少量存在的各种雌激素化合物的活性。
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