Normal human thyroid cells from the ARAMIS line follow the general concept of growth or differentiation: a study with thyroglobulin as a marker.

Abstract

A cell line of functional normal human adult thyroid cells was isolated 3 years ago. This cell line was used as a model to study human thyroglobulin (hTgb) production quantified in 5% fetal calf serum Click-RPMI medium and in the presence of insulin and thyrotropin (two hormones [2H]) to get maximal hTgb production. In this paper we demonstrate that these cells (line ARAMIS) follow the general dualistic opposition between growth and differentiation. Thyroglobulin cell production in 2H-stimulated cells is dependent on cell density and is not constant with time of culture in growing and in quiescent cells. High serum levels required for cell proliferation antagonize thyroglobulin cell production. Furthermore, in the absence of cell proliferation, the longer the cells stay in the stationary phase in 2H-medium, the better they produce thyroglobulin with time. The longer the cells stay in the stationary phase in 1H (insulin) medium, the higher will be the total thyroglobulin production and the initial rate in thyroglobulin production after TSH addition. The longer the cells stay in the stationary phase in 1H (insulin) medium, the higher are cyclic adenosine monophosphate (cAMP) levels after thyrotropin (TSH) stimulation. This is observed both for initial rates and total production. Neither insulin nor cell-cell interactions occurring during the stationary phase modify basal cAMP levels. Altogether the data demonstrate that in cell culture conditions that exclude proliferation, a gain in TSH sensitivity appears versus time in insulin-stimulated quiescent normal human thyroid cells during their stationary phase. This improved differentiating status appears to be TSH- and cAMP-independent. It could be an insulin or insulin-like growth factor-1 (IGF-1)-dependent trophic effect promoting an increase in TSH-receptor number or sensitivity. But once again and as mentioned previously, we cannot exclude from the data that cell to cell interactions between silent and "informed" cells (in other words, autocrine phenomena) could result, with time, in the recruitment of silent resting cells, explaining the gain in TSH sensitivity.