Thyroid-stimulating hormone transcriptionally: Regulates the thiol-specific antioxidant gene

Thiol-specific antioxidant (TSA) plays an important role in regulating cell differentiation and proliferation by modulating the hydrogen peroxide (H2O 2) mediated responses in a variety of mammalian cells. Thyroid cells are co nstantly exposed to the actions of reactive oxygen species (ROS), because t hey produce high levels of H2O2 in response to the physiological action of TSH (thyroid-stimulating hormone). Thyrocytes have several defense mechanis ms against ROS, including TSA and SOD (superoxide anion dismutase). Using N orthern blot hybridization, we tested the effects of TSH on TSA gene expres sion in FRTL-5 cells derived from rat thyroids. TSA mRNA expression increas ed following treatment of cells with TSH at concentrations greater than 10( -9) M. This effect was observed within 6 hours following treatment, and pea ked at 8 hours. The effect was blocked by actinomycin D, but not by cyclohe ximide. The half-life of TSA mRNA was approximately 5.5 hours in the presen ce or absence of TSH, and that was not affected by TSA mRNA stability. The effects on TSA gene expression were specific to TSH. Other growth factors ( e.g., insulin, transferrin and hydrocortisone) did not alter TSA expression . Our results are the first indication that TSH regulates the expression of TSA transcriptionally in thyrocytes. Copyright (C) 2001 S. Karger AG, Base l.