Thyrotrophin and the differential expression of proliferation and differentiation in dog thyroid cells in primary culture.

Cell proliferation and the expression of differentiated functions are generally considered to be mutually exclusive states of the cell. Thyrotrophin activates the expression of differentiated functions in dog thyroid cells by means of cyclic AMP. We have recently shown that thyrotrophin also acts through the same intracellular signal molecule to enhance proliferation of dog thyroid cells in primary cultures. In this work we showed that such primary cultures exhibit three successive phases: a latency period during which the expression of differentiated functions (iodide trapping and organification) declined, the cells still being associated with structures derived from the seeded follicles; a cell-proliferation phase with little expression of these functions, the cells being spread in a monolayer; a stationary phase with cell density reaching a plateau but no re-expression of the functions. Thyrotrophin promoted proliferation during the multiplication phase, but induced redifferentiation during the stationary phase. These effects were mimicked by cholera toxin and dibutyryl cyclic AMP, which suggested that they were mediated by cyclic AMP. Iodide uptake was also stimulated by cortisol. Thyrotrophin therefore has a different action in dog thyroid cells depending on the state of the cells. The spontaneous arrest of multiplication appears to make the cells competent to respond to thyrotrophin by the induction of redifferentiation.