ArticleEnvironmental health perspectives2016
In Vitro Effects of the Endocrine Disruptor p,p'-DDT on Human Follitropin Receptor.
Article in Environmental health perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Cytomolecular and In Vitro Toxicity Studies on Bisphenol A Effect on Ovine Granulosa Cells.Veterinary medicine international · 2026Article
- Beyond the Nucleus: Plastic Chemicals Activate G Protein-Coupled Receptors.Environmental science & technology · 2024Article
- [Advances in the applications of exposomics in the identification of environmental pollutants and their health hazards].Se pu = Chinese journal of chromatography · 2024Article
- Allosteric modulation of gonadotropin receptors.Frontiers in endocrinology · 2023Review
- Endocrine Disrupting Chemicals' Effects in Children: What We Know and What We Need to Learn?International journal of molecular sciences · 2022Review
- In vitro effects of the endocrine disruptor p,p'DDT on human choriogonadotropin/luteinizing hormone receptor signalling.Archives of toxicology · 2021Article
- Endocrine Disruption of the Follicle-Stimulating Hormone Receptor Signaling During the Human Antral Follicle Growth.Frontiers in endocrinology · 2021Review
- Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification.Nature reviews. Endocrinology · 2020Review
- Upregulation of vitamin D-binding protein is associated with changes in insulin production in pancreatic beta-cells exposed to p,p'-DDT and p,p'-DDE.Scientific reports · 2019Article
- Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells.Frontiers in pharmacology · 2019Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background1-chloro-4-[2,2,2-trichloro-1-(4-chlorophenyl)ethyl]benzene (p,p'-DDT) is a persistent environmental endocrine disruptor (ED). Several studies have shown an association between p,p'-DDT exposure and reproductive abnormalities.
objectivesTo investigate the putative effects of p,p'-DDT on the human follitropin receptor (FSHR) function. METHODS AND
resultsWe used Chinese hamster ovary (CHO) cells stably expressing human FSHR to investigate the impact of p,p'-DDT on FSHR activity and its interaction with the receptor. At a concentration of 5 μM p,p'-DDT increased the maximum response of the FSHR to follitropin by 32 ± 7.45%. However, 5 μM p,p'-DDT decreased the basal activity and did not influence the maximal response of the closely related LH/hCG receptor to human chorionic gonadotropin (hCG). The potentiating effect of p,p'-DDT was specific for the FSHR. Moreover, in cells that did not express FSHR, p,p'-DDT had no effect on cAMP response. Thus, the potentiating effect of p,p'-DDT was dependent on the FSHR. In addition, p,p'-DDT increased the sensitivity of FSHR to hCG and to a low molecular weight agonist of the FSHR, 3-((5methyl)-2-(4-benzyloxy-phenyl)-5-{[2-[3-ethoxy-4-methoxy-phenyl)-ethylcarbamoyl]-methyl}-4-oxo-thiazolidin-3-yl)-benzamide (16a). Basal activity in response to p,p'-DDT and potentiation of the FSHR response to FSH by p,p'-DDT varied among FSHR mutants with altered transmembrane domains (TMDs), consistent with an effect of p,p'-DDT via TMD binding. This finding was corroborated by the results of simultaneously docking p,p'-DDT and 16a into the FSHR transmembrane bundle.
conclusionp,p'-DDT acted as a positive allosteric modulator of the FSHR in our experimental model. These findings suggest that G protein-coupled receptors are additional targets of endocrine disruptors. CITATION: Munier M, Grouleff J, Gourdin L, Fauchard M, Chantreau V, Henrion D, Coutant R, Schiøtt B, Chabbert M, Rodien P. 2016. In vitro effects of the endocrine disruptor p,p'-DDT on human follitropin receptor. Environ Health Perspect 124:991-999; http://dx.doi.org/10.1289/ehp.1510006.
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