Modulation of differentiated function in cultured thyroid cells: thyrotropin control of thyroid peroxidase activity

The activity of thyroid peroxidase (TPO) in primary dog thyroid cell cultures was measured by both guaiacol oxidation and iodide oxidation assays. Whether cultures were initiated in the absence or presence of 50 mU/ml TSH, TPO activity fell in the first 24 h of culture to approximately 10% of the activity in freshly isolated follicles. After 5 days in culture, TPO activity almost completely disappeared in the absence of TSH, whereas in the presence of TSH, TPO activity rebounded to approximately 30% of that in freshly isolated follicles. TSH similarly induced TPO activity in cells that had lost this activity during a 1- to 6-day preincubation period in the absence of hormone. The half-time for the induction of TPO activity was approximately 3 days. Whether TSH was present from the start of culture or added after 5 days of culture without TSH, the half-maximal dose for reinduction of TPO activity was 0.3-0.4 mU TSH/ml. (Bu)2cAMP, 8-bromo-cAMP, forskolin, and cholera toxin all mimicked, either completely or in part, the ability of TSH to induce TPO activity in cells preincubated without hormone. We conclude that, in cultured dog thyroid cells, TPO activity is modulated by chronic TSH stimulation, and that this effect is mediated by cAMP. However, even though TSH stimulates TPO activity in cultured thyroid cells, the fact that there is no comparable restoration of organic iodine formation (as found in previous studies) makes it likely that other aspects of the iodide organification mechanism are altered.