Abstract
Polychlorinated biphenyls (PCBs) can disrupt the endocrine function, promote neoplasms and regulate apoptosis in some tissues; however, it is unknown whether PCBs can affect the apoptosis of pituitary cells. The study evaluated the effect of PCBs on the apoptosis of normal pituitary cells and the underlying mechanisms. Primary cell cultures obtained from mouse pituitary glands were exposed to Aroclor 1254 or selected dioxin-like (PCB 77, PCB 126) or non-dioxin-like (PCB 153, PCB 180) congeners. Apoptosis was evaluated by Annexin V staining, DNA fragmentation, and TUNEL assay. Both the expression and activity of caspases were analyzed. Selective thyroid hormone receptor (TR) or aryl-hydrocarbon receptor (AhR) or CYP1A1 antagonist were used to explore the mechanisms underlying PCBs action. Our results showed that Aroclor 1254 induced the apoptosis of pituitary cells as well as the final caspase-3 level and activity through the extrinsic pathway, as shown by the increased caspase-8 level and activity. On the other hand, the intrinsic pathway evaluated by measuring caspase-9 expression was silent. The selected non-dioxin-like congeners either increased (PCB 180) or reduced (PCB 153) pituitary cell apoptosis, affecting the extrinsic pathway (PCB 180), or both the extrinsic and intrinsic pathways (PCB 153), respectively. In contrast, the dioxin-like congeners (PCB 77 and PCB 126) did not affect apoptosis. The anti-apoptotic phenotype of PCB 153 was counteracted by a TR or a CYP1A1 antagonist, whereas the pro-apoptotic effect of PCB 180 was counteracted by an AhR antagonist. The induced apoptosis of Aroclor 1254 or PCB 180 was associated with a reduction of cell proliferation, whereas the decreased apoptosis due to PCB 153 increased cell proliferation by 30%. In conclusion, our data suggest that non-dioxin-like PCBs may modulate apoptosis and the proliferation rate of pituitary cells that have either pro- or anti-apoptotic effects depending on the specific congeners. However, the impact of PCBs on the process of pituitary tumorigenesis remains to be elucidated.
Highlights
IntroductionThere is increasing evidence that the hypothalamic-pituitary axis may be targeted by chemicals with endocrine disruption activities [4]
Polychlorinated biphenyls (PCBs) are persistent pollutants, which can disrupt the endocrine function [1], and promote the incidence of tumors [2, 3].There is increasing evidence that the hypothalamic-pituitary axis may be targeted by chemicals with endocrine disruption activities [4]
The non-dioxin-like congeners seem to be responsible for the changes in apoptosis of the pituitary cells exposed to PCBs
Summary
There is increasing evidence that the hypothalamic-pituitary axis may be targeted by chemicals with endocrine disruption activities [4]. Dioxin and some PCBs with a dioxin-like structure may bind to the aryl-hydrocarbon receptor (AhR) [8]. Some PCBs with a non-dioxin-like structure can activate or suppress the gene expression regulated by the thyroid hormone, interacting with the thyroid hormone receptor (TR) [9]. In addition to the disruption of the endocrine function through the direct interaction with hormone receptors, PCBs can affect the endocrine system by modulating apoptosis [10]. Little information is available concerning the influence of PCBs on apoptosis in the endocrine system, and in the pituitary. It has been reported that in testes the nondioxin-like PCB 132 may reduce apoptosis at low concentrations, and increase apoptosis at high doses [11]
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