TLR-4 signaling pathway mediates LPS-induced proliferation of hyperplastic lactotrophs cells

SABATINO ME; GUTIÉRREZ S; MASCANFRONI I; SOSA L; PETITI JP; MUKDSI JH; TORRES AI; DE PAUL AL

Huerta Grande

Workshop; II Reunión Conjunta de Neurociencias; 2010

Sociedad Argentina de Neurociencia

Intrapituitary cytokines production stimulated by lipopolysaccharide (LPS) activates HPA axis during pathological events. LPS is recognized by the TLR-4, which is involved in cancer progression. Previously we showed that LPS induced lactotroph proliferation in estrogen-stimulated hyperplastic glands in vitro. In this work we studied TRL-4 presence on lactotrophs and the intracellular mechanism involved in response to LPS. Male rats were treated with or without estradiol benzoate for 60 days. Then, anterior pituitary glands were cultured and stimulated for 30min with LPS (100ng/ml). Statistic analysis: ANOVA-Fisher Test. TLR-4 localization in hyperplastic lactotrophs was confirmed for the first time by flow cytometry and confocal microscopy. Also, we observed a significant increase in TLR-4/CD14 expression, Akt and Erk1/2 activation and NF-kB nuclear translocation in response to LPS by western blot. Although, TLR-4 was found in normal lactotrophs, BrdU incorporation revealed no effects of LPS on these cells proliferation. Concluding, hyperplastic lactotrophs respond to LPS by activating TLR-4/CD14, Akt, Erk1/2 and NFkB to elicit cell proliferation. Estrogenic priming might influence lactotroph sensivity to LPS, promoting proliferative injury.