In order to provide a global analysis of the effects of endocrine disruptors on the hormone cellular bioavailability, we combined 17beta-estradiol (E2) cellular flow studies with real-time PCR and Western blot expression measurements of genes involved in the hormone metabolism and excretion. Three endocrine disruptors commonly found in food were chosen for this study, which was conducted in the estrogen receptor (ER) negative hepatoblastoma HepG2 cell line: bisphenol A (BPA), genistein (GEN) and resveratrol (RES). We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention. Thus, we demonstrate that bisphenol A, genistein and resveratrol modulate 17beta-estradiol cellular bioavailability in HepG2 and that these modulations most probably involve regulations of 17beta-estradiol phase II and III metabolism proteins. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to ERs. Our results obtained with ER negative cells provide strong evidence for the existence of ER-independent pathways leading to endocrine disruption.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.steroids.2008.06.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sex differences in aristolochic acid I-induced nephrotoxicity in mice and the effect of estradiol.
Toxicol Appl Pharmacol
January 2025
School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; Luzhou New Drug Evaluation and Research Center, Luzhou, Sichuan 646000, China. Electronic address:
Aristolochic acid I (AAI), the most prominent component of aristolochic acids and found in nearly all aristolochic herbs, has been demonstrated significant nephrotoxicity. In this study, an acute nephrotoxicity model of AAI mice was established by a single dose injection of AAI. It was observed that there are differences of the sensitivity to AAI nephrotoxicity in female and male mice, with male mice exhibiting nephrotoxic effects even at lower doses.
View Article and Find Full Text PDFSexual dimorphism in right ventricular adaptation to pressure overload involves differential angiogenic response.
Am J Physiol Heart Circ Physiol
January 2025
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS.
This study investigated the sexual dimorphism in right ventricle (RV) remodeling in right heart failure susceptible Fischer CDF rats using the pulmonary artery banding (PAB) model. Echocardiography and hemodynamic measurements were performed in adult male and female Fischer CDF rats at 1- or 2-weeks post-PAB. RV systolic pressure and RV hypertrophy were significantly elevated in PAB rats compared to sham control at 1- and 2-weeks post-PAB; however, no differences were observed between male and female rats.
View Article and Find Full Text PDFIncreases in the susceptibility of human endometrial CD4 T cells to HIV-1 infection post-menopause are not dependent on greater viral receptor expression frequency.
Front Immunol
January 2025
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
Epidemiological evidence suggests that post-menopausal women are more susceptible to HIV infection following sexual intercourse than are younger cohorts for reasons that remain unclear. Here, we evaluated how menopause-associated changes in CD4 T cell numbers and subsets as well as HIV coreceptor expression, particularly CCR5, in the endometrium (EM), endocervix (CX), and ectocervix (ECX) may alter HIV infection susceptibility. Using a tissue-specific mixed cell infection model, we demonstrate that while no changes in CD14 macrophage infection susceptibility were observed, CD4 T cell HIV-1 infection frequency increases following menopause in the EM, but not CX nor ECX.
View Article and Find Full Text PDFDecreased lymph node estrogen levels cause nonremitting progressive experimental autoimmune encephalomyelitis disease.
PNAS Nexus
January 2025
Department of Comparative Biosciences, The University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802, USA.
Estrogen, a steroid hormone synthesized by both gonadal and nongonadal tissues, plays a pivotal role in modulating immune responses, including reducing relapse rates in relapsing-remitting multiple sclerosis (MS). This study explored the expression of aromatase, the enzyme responsible for estrogen synthesis, in lymph nodes (LNs) and its potential role in the pathogenesis of MS using a mouse model. We utilized Cyp19-RFP mice where cells that express or have previously expressed the Cyp19 gene (encoding aromatase) are marked by red fluorescent protein (RFP).
View Article and Find Full Text PDFFormononetin ameliorates polycystic ovary syndrome through suppressing NLRP3 inflammasome.
Mol Med
January 2025
Reproduction and Genetics Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42 Wenhua West Road, Lixia District, Jinan, 250014, Shandong, China.
Background: Polycystic ovary syndrome (PCOS) is a common gynecological disease accompanied by multiple clinical features, including anovulation, hyperandrogenism, and polycystic ovarian morphology, leading to infertility. Formononetin (FMN), which is a major bioactive isoflavone compound in Astragalus membranaceus, exerts anti-inflammatory effects. However, whether FMN is effective in the treatment of PCOS remains unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!