Abstract
PurposeEndocrine disruptors are known to modulate a variety of endocrine functions and increase the risk for neoplasia. Epidemiological data reported increased prevalence of pituitary tumors in high industrial areas while genotyping studies showed that mutations in the aryl hydrocarbon receptor (AhR) interacting protein (AIP)—chaperone to the dioxin ligand AhR—gene are linked to predisposition to pituitary tumor development. Aim of the present study was to establish whether endocrine pollutants can induce cell proliferation in normal rat pituitary cells.MethodsPituitary primary cultures were incubated with 250, 650 and 1250 pM benzene or 2-ethyl-phthalate for up to 96 h and viability, energy content and cell proliferation assessed. Expression of pituitary tumor transforming gene (PTTG), cyclin D1 (Ccnd1), AhR and AIP was quantified by RT-qPCR.ResultsIncubation with benzene or 2-ethyl-phthalate increased viability and energy content in pituitary cells. The endocrine disruptors also increased cell proliferation as well as Ccnd1 and PTTG expression. Increased AhR and AIP expression was observed after incubation with the two pollutants.ConclusionsOur findings indicate that benzene and 2-ethyl-phthalate activate AhR/AIP expression and stimulate proliferation in normal rat pituitary cells. This study is the first demonstration that pollutants can induce normal pituitary cells to proliferate and provides a link between epidemiological and genomic findings in pituitary tumors.
Highlights
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Endocrine disruptors are widely distributed chemical pollutants known to affect endocrine functions [1, 2], in particular reproduction and development
Epidemiological data reported increased prevalence of pituitary tumors in high industrial areas while genotyping studies showed that mutations in the aryl hydrocarbon receptor (AhR) interacting protein (AIP)— chaperone to the dioxin ligand AhR—gene are linked to predisposition to pituitary tumor development
Expression of pituitary tumor transforming gene (PTTG), cyclin D1 (Ccnd1), AhR and Aryl hydrocarbon receptor-interacting protein (AIP) was quantified by RT-qPCR
Summary
Electronic supplementary material The online version of this article (doi:10.1007/s11102-016-0777-3) contains supplementary material, which is available to authorized users.Endocrine disruptors are widely distributed chemical pollutants known to affect endocrine functions [1, 2], in particular reproduction and development. The carcinogenic potential of endocrine disruptors has become a major research focus following epidemiological data showing an association between endocrine disruptor exposure and breast, prostate, testis and thyroid neoplasia [6,7,8,9,10]. In support of this evidence, in vitro studies showed that endocrine disruptors induce cell cycle deregulation, death and proliferation in breast and ovarian cancer cell lines [11,12,13]. Similar growthpromoting effects have been reported for estrogensensitive pituitary adenoma cell lines, e.g. MtT/E2 [14, 15], Pituitary (2017) 20:311–318
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