THYROTROPIN IS NOT A GROWTH-FACTOR FOR HUMAN THYROID-CELLS IN CULTURE

Thyroid cells, obtained from both normal human tissue and benign nodular goiter, were cultured and maintained in vitro in 4-18 passages. Cultures with confluent cells accumulated cyclic AMP (10-150 times the basal amount) upon addition of bovine thyrotropin (100 milliunits/ml), indicating that the cells in culture maintained a thyrotropin-sensitive adenylate cyclase system. Addition of high doses of thyrotropin also induced a characteristic and reversible change in the morphology of the cells. The effect of thyrotropin on cell growth was studied in short- and long-term experiments. Thyrotropin reduced [3H]thymidine incorporation in a dose-dependent fashion in all cultures of thyroid cells. The maximal inhibition over a 24-hr period was about 50%. The thyroid cells were notably sensitive, and the half-maximal effect occurred at about 100 milliunits of thyrotropin per ml. In contrast, the hormone had no effect on [3H]thymidine incorporation into human glial cells. Low doses of thyrotropin also had no effect on human fibroblasts and, at high doses, a stimulation of [3H]thymidine incorporation was seen. Thyroid cell cultures grown in the presence of 10 milliunits of thyrotropin per ml for 7-14 days had a slower growth rate and 24-36% lower cell numbers at saturation density than control dishes, indicating that the hormone also had a long-term effect on cell proliferation. The data agree with in vitro studies by others of the effects of corticotropin and lutropin on target cells and suggest that in vivo the primary action of pituitary trophic hormones on endocrine tissues is not stimulation of growth.