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.