Inhibition of Nuclear Factor-Kappa B Sensitises Anterior Pituitary Cells to Tumour Necrosis Factor-α- and Lipopolysaccharide-Induced Apoptosis

• Published in: Journal of neuroendocrinology 2011-08, Vol.23 (8), p.651-659
• Main Authors: Eijo, G., Zárate, S., Jaita, G., Ferraris, J., Magri, M. L., Zaldivar, V., Radl, D., Boti, V., Pisera, D., Seilicovich, A.
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Animals; Apoptosis; Apoptosis - drug effects; Bcl-x protein; Biological and medical sciences; Cell culture; Cell survival; Cells, Cultured; DNA nucleotidylexotransferase; Estradiol - pharmacology; Estrogens; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; Inflammation; lactotroph; Lipopolysaccharides; Lipopolysaccharides - pharmacology; LPS; NF- Kappa B protein; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; Nitriles - pharmacology; Nuclear transport; oestrogens; Ovariectomy; pituitary; Pituitary (anterior); Pituitary Gland, Anterior - cytology; Rats; Rats, Wistar; Signal transduction; Signal Transduction - drug effects; somatotroph; Sulfones - pharmacology; TNF-α; Tumor necrosis factor- alpha; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: endocrinology; Western blotting
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2011.02157.x

Nuclear factor‐kappa B (NF‐κB), an important pro‐inflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumour necrosis factor (TNF)‐α activate NF‐κB signalling. Oestrogens were shown to suppress NF‐κB activation. Oestrogens exert a sensitising action to pro‐apoptotic stimuli such as LPS and TNF‐α in anterior pituitary cells. In the present study, we show by western blotting that 17β‐oestradiol (E2) decreases TNF‐α‐induced NF‐κB/p65 and p50 nuclear translocation in primary cultures of anterior pituitary cells from ovariectomised (OVX) rats. Also, the in vivo administration of E2 decreases LPS‐induced NF‐κB/p65 and p50 nuclear translocation. To investigate whether the inhibition of NF‐κB pathway sensitises anterior pituitary cells to pro‐apoptotic stimuli, we used an inhibitor of NF‐κB activity, BAY 11‐7082 (BAY). BAY, at a concentration that fails to induce apoptosis, has permissive action on TNF‐α‐induced apoptosis of lactotrophs and somatotrophs from OVX rats, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Pharmacological inhibition of NF‐κB signalling enhances E2‐sensitising effect to TNF‐α‐induced apoptosis in lactotrophs but not in somatotrophs. In vivo administration of BAY allowed LPS‐induced apoptosis in anterior pituitary cells from OVX rats (determined by fluorescence activated cell sorting). Furthermore, LPS‐induced expression of Bcl‐xL in pituitaries of OVX rats is decreased by E2 administration. Our results show that inhibition of the NF‐κB signalling pathway sensitises anterior pituitary cells to the pro‐apoptotic action of LPS and TNF‐α. Because E2 inhibits LPS‐ and TNF‐α‐activated NF‐κB nuclear translocation, the present study suggests that E2 sensitises anterior pituitary cells to TNF‐α‐ and LPS‐induced apoptosis by inhibiting NF‐κB activity.