{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:40:16Z","timestamp":1791420016703,"version":"4.3.3"},"reference-count":66,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":3243,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fetal exposure to environmental estrogens may contribute to hypofertility and\/or to testicular germ cell cancer. However, many of these xenoestrogens have only a weak affinity for the classical estrogen receptors (ERs,) which is 1,000-fold less potent than the affinity of 17\u03b2-estradiol (E2). Thus, several mechanisms have been suggested to explain how they could affect male germ cell proliferation at low environmental relevant concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In this study we aimed to explore the possible promoting effect of bisphenol A (BPA) on human testicular seminoma cells. BPA is a well-recognized estrogenic endocrine disruptor used as a monomer to manufacture poly carbonate plastic and released from resin-lined food or beverage cans or from dental sealants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>BPA at very low concentrations (10\u22129 to 10\u221212 M) similar to those found in human fluids stimulated JKT-1 cell proliferation in vitro. BPA activated both cAMP-dependent protein kinase and cGMP-dependent protein kinase pathways and triggered a rapid (15 min) phosphorylation of the transcription factor cAMP response-element\u2013binding protein (CREB) and the cell cycle regulator retinoblastoma protein (Rb). This nongenomic activation did not involve classical ERs because it could not be reversed by ICI 182780 (an ER antagonist) or reproduced either by E2 or by diethylstilbestrol (a potent synthetic estrogen), which instead triggered a suppressive effect. This activation was reproduced only by E2 coupled to bovine serum albumin (BSA), which is unable to enter the cell. As with E2-BSA, BPA promoted JKT-1 cell proliferation through a G-protein\u2013coupled nonclassical membrane ER (GPCR) involving a G\u03b1s and a G\u03b1i\/G\u03b1q subunit, as shown by the reversible effect observed by the corresponding inhibitors NF449 and pertussis toxin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This GPCR-mediated nongenomic action represents\u2014in addition to the classical ER-mediated effect\u2014a new basis for evaluating xenoestrogens such as BPA that, at low doses and with a high affinity for this GPCR, could interfere with the developmental programming of fetal germ cell proliferation and\/or differentiation when they cross the placenta.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1289\/ehp.0800367","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T14:14:37Z","timestamp":1234275277000},"page":"1053-1058","source":"Crossref","is-referenced-by-count":253,"title":["Low Doses of Bisphenol A Promote Human Seminoma Cell Proliferation by Activating PKA and PKG via a Membrane G-Protein\u2013Coupled Estrogen Receptor"],"prefix":"10.1021","volume":"117","author":[{"given":"Adil","family":"Bouskine","sequence":"first","affiliation":[{"name":"Institut National de la recherch\u00e9 M\u00e9dicale (INSERM) U895, Team 5\u2014Environment and Reproduction: Genomic and Nongenomic Mechanisms, University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Nebout","sequence":"additional","affiliation":[{"name":"Institut National de la recherch\u00e9 M\u00e9dicale (INSERM) U895, Team 5\u2014Environment and Reproduction: Genomic and Nongenomic Mechanisms, University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Br\u00fccker-Davis","sequence":"additional","affiliation":[{"name":"Institut National de la recherch\u00e9 M\u00e9dicale (INSERM) U895, Team 5\u2014Environment and Reproduction: Genomic and Nongenomic Mechanisms, University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France"},{"name":"Department of Reproductive Endocrinology, University Hospital of Nice, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Benahmed","sequence":"additional","affiliation":[{"name":"Institut National de la recherch\u00e9 M\u00e9dicale (INSERM) U895, Team 5\u2014Environment and Reproduction: Genomic and Nongenomic Mechanisms, University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Fenichel","sequence":"additional","affiliation":[{"name":"Institut National de la recherch\u00e9 M\u00e9dicale (INSERM) U895, Team 5\u2014Environment and Reproduction: Genomic and Nongenomic Mechanisms, University of Nice-Sophia-Antipolis, Faculty of Medicine, Nice, France"},{"name":"Department of Reproductive Endocrinology, University Hospital of Nice, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2009,2,11]]},"reference":[{"issue":"13","key":"2026080413035995700_micit1","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.1523\/JNEUROSCI.23-13-05771.2003","article-title":"Estrogen receptor beta mediates rapid estrogen actions on gonadotropin-releasing hormone neurons in vivo","volume":"23","author":"Abraham","year":"2003","journal-title":"J 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