Lipopolysaccharide stimulates adrenal steroidogenesis in rodent cells by a NFkB dependent mechanism involving COX-2 activation

MARTINEZ CALEJMAN C; ASTORT F; DI GRUCCIO JM; REPETTO EM; MERCAU M; GIORDANINO EF; SANCHEZ R; PIGNATARO O; ARIAS P; CYMERYNG CB

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2011 vol. 337 p. 1 - 6

0303-7207

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 NFkB 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. NFkB activity and COX-2 protein levels are increased in this cell line by LPS treatment, and pharmacologic and molecular manipulation of the NFkB 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 NFkB signaling pathway and the induction of COX-2.