TONIC MODULATION OF DOG THYROCYTE H2O2 GENERATION AND I- UPTAKE BY THYROTROPIN THROUGH THE CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE CASCADE

The dog thyrocyte I- trapping activity and the expression of the genes coding for dog thyrocyte thyroglobulin or thyroid peroxidase are enha nced by TSH through the cAMP cascade and reduced by mitogens such as e pidermal growth factor (EGF) or 12-O-tetradecanoylphorbol 13-acetate ( TPA). In this work, we investigated whether H2O2 generation (a limitin g step of thyroid hormone synthesis) is modulated by chronic treatment of the thyrocyte with TSH or mitogens such as EGF or TPA. We observed that both basal and carbachol- or ionomyein-stimulated H2O2 generatio n by the dog thyrocyte were concentration and time dependently enhance d by prolonged (12- to 72-h) exposure to TSH. This effect was reproduc ed by agents that increase the dog thyrocyte cAMP level or that mimic this increase. It was abolished when protein or RNA synthesis was inhi bited. By contrast, EGF and TPA concentration and time dependently ant agonized the effect of TSH. In addition, chronic exposure to EGF reduc ed both basal and carbachol- or ionomycin-stimulated H2O2 generation. The effect of TPA was reproduced by another protein kinase-C activatin g phorbol eater, phorbol dibutyrate, but not by beta-phorbol, an inact ive phorbol eater. Modulation of dog thyrocyte H2O2 generation by chro nic exposure to TSH or to the mitogens EGF and TPA was totally paralle l to the modulation of their I-125(-) uptake. Taken together our resul ts suggest that H2O2 generation (or at least one of its constituents) is a differentiation characteristic of the dog thyrocyte under tonic c ontrol of TSH through the cAMP cascade as iodide transport, thyroid pe roxidase, and thyroglobulin.