The plateau phase rat goiter contains a sub-population of TSH-responsive follicular cells capable of proliferation following transplantation

Abstract

In the rat, chronic TSH stimulation leads to self-limited thyroid hyperplasia, goitrogenesis, and TSH-responsive thyroid tumors. The current studies were aimed at clarifying the mechanism by which hormone-responsive, proliferating follicular cells arise in quiescent plateau phase rat goiters. Enzymatically monodispersed rat thyrocytes from early plateau phase and involuting goiters were analyzed for the capacity to form thyroid follicular units after transplantation into syngeneic recipients. Goiters induced with two different regimens contained substantial numbers of cells capable of proliferating into functioning thyroid follicular tissue after transplantation. The clonogenic fractions of cells from goiters induced by 3-amino-1,2,4-triazole or KClO4/Remington low iodine diet were significantly lower than that of cells from control glands. Furthermore, the clonogenic fraction of cells from the KClO4 goiters was also found to be significantly less than that of cells from aminotriazole goiters despite similar TSH levels in the cell donors. The hormone responsiveness of the clonogenic goiter cells and the histological appearance and functional capacity of the thyroid tissue which arose after grafting were indistinguishable from controls. We conclude that the capacity to clonally proliferate into follicular units is a specific trait which characterizes a unique subset of follicular cells and speculate that the hormone-responsive tumors which typically appear in the chronically stimulated rat thyroid originate from cells within this subset.