Effects of ceramide and protein kinase C on the regulation of type I 5'-deiodinase in FRTL-5 rat thyroid cells

Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine that is involved in the regulation of thyroid growth and differentiated functions. The cellular and molecular mechanisms involved in mediating the effects of TNF alpha on thyroid function, however, are unknown. In a number of cell types, TNF alpha receptor binding results in the activation of specific signal transduction cascades, including protein kinase C (PKC) and the hydrolysis of sphingomyelin to ceramide. In the present study, we examined the possible role of PKC and the hydrolysis of sphingomyelin to ceramide in the regulation of TSH-induced increases in 5'-deiodinase (5'D-I) activity and 5'D-I messenger RNA (mRNA) levels in FRTL-5 cells. Further, we have recently shown that TNF alpha and interferon-gamma (IFN gamma) act synergistically to block TSH-induced increases in type I 5'D-I activity and 5'D-I gene expression in FRTL-5 rat thyroid cells. Thus, we tested the hypothesis that the activation of one or both pathways is involved in...