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Publication : Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation.

First Author  Martinez Calejman C Year  2011
Journal  Mol Cell Endocrinol Volume  337
Issue  1-2 Pages  1-6
PubMed ID  21300135 Mgi Jnum  J:179463
Mgi Id  MGI:5302457 Doi  10.1016/j.mce.2010.12.036
Citation  Martinez Calejman C, et al. (2011) Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFkappaB-dependent mechanism involving COX-2 activation. Mol Cell Endocrinol 337(1-2):1-6
abstractText  Stimulation of adrenal steroidogenesis is involved in the HPA response to exogenous noxa. Although inflammatory cytokines can mediate the LPS-triggered activation of the HPA, direct effects of LPS on glucocorticoid release have been described. Present studies were undertaken to characterize the molecular mechanisms underlying the effect of LPS on steroid secretion in isolated rodent adrenal cells, assessing the participation of NFkappaB and COX-2 activities in this response. Our results show that LPS treatment stimulates steroidogenesis in murine and rat adrenocortical cells, and that Y1 cells express the binding-transducing complex TLR-4/CD14/MD-2, as demonstrated by RT-PCR. NFkappaB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFkappaB pathway significantly affected both COX-2 protein levels and steroid production. Finally, pharmacological inhibition of COX-2 activity significantly impairs steroid production. Thus, our results strongly suggest that the mechanism involved in the stimulation of steroidogenesis by LPS in rodent adrenal cells involves the activation of the NFkappaB signaling pathway and the induction of COX-2.
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