title: Divergent Effects of Dioxin- or Non-Dioxin-Like Polychlorinated Biphenyls on the Apoptosis of Primary Cell Culture from the Mouse Pituitary Gland.
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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Raggi
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Dania
authors.initials: D
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Urbani
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sardella
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Manetti
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cappellani
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Lupi
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Tomisti
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000737:chemistry; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D053938:DNA Fragmentation; D004147:Dioxins / Q000009:adverse effects / Q000737:chemistry*; D004703:Endocrine System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010641:Phenotype; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000009:adverse effects / Q000737:chemistry*; D061251:Primary Cell Culture; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017304:Annexin A5; D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D011988:Receptors, Thyroid Hormone; C410127:PCB 180; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; C023035:3,4,5,3',4'-pentachlorobiphenyl; C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl