title: Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFκB-dependent mechanism involving COX-2 activation.
abstract: 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 NFκB 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. NFκB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFκB 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 NFκB signaling pathway and the induction of COX-2.
authors.affiliation: Department of Human Biochemistry, School of Medicine, University of Buenos Aires/CEFYBO-CONICET, Paraguay, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Martinez Calejman
authors.forename: F
authors.initials: F
authors.lastname: Astort
authors.forename: J M
authors.initials: JM
authors.lastname: Di Gruccio
authors.forename: E M
authors.initials: EM
authors.lastname: Repetto
authors.forename: M
authors.initials: M
authors.lastname: Mercau
authors.forename: E
authors.initials: E
authors.lastname: Giordanino
authors.forename: R
authors.initials: R
authors.lastname: Sanchez
authors.forename: O
authors.initials: O
authors.lastname: Pignataro
authors.forename: P
authors.initials: P
authors.lastname: Arias
authors.forename: C B
authors.initials: CB
authors.lastname: Cymeryng
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; C456319:PS1145; D010750:Phosphoproteins; D011725:Pyridines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D003345:Corticosterone