Mitogenic effects of thyrotropin and adenosine 3',5'-monophosphate in differentiated normal human thyroid cells in vitro.

摘要: Previous studies of human thyroid cells in culture (mostly from pathological tissues) failed to demonstrate a mitogenic effect TSH, leading the proposal that growth TSH vivo might be indirect. To reexamine influence on DNA synthesis and cell proliferation, we established primary cultures normal tissue nine subjects. When seeded 1% serum-supplemented medium, follicles released by collagenase/dispase digestion developed as monolayer responded rounding up cytoplasmic retraction. serum-free remained associated dense aggregates surrounded few slowly spreading cells. In latter condition, other stimulators cAMP production, such cholera toxin forskolin, displaying very high iodide-trapping levels. Exposure serum irreversibly abolished this differentiated function. stimulated proliferation (as shown content per dish) cultured (doubling times were reduced 106 76 h) increased 100% [3H]thymidine labeling indices. (dense or monolayers after initial seeding with serum), control levels lower, 8-fold stimulation occurred response 100 mU/L (stimulation was consistently detected 20 mU/L), based measurements incorporation into acid-precipitable material counts labeled nuclei autoradiographs (up 40% within 24 h). The required insulin concentration (8.3 X 10(-7) mol/L) low insulin-like factor I concentration. effects mimicked part toxin, dibutyryl cAMP. Epidermal phorbol myristate ester also synthesis, but they potently inhibited TSH-stimulated iodide transport. We conclude acting at least through cAMP, is potent for thus provide an experimental basis vitro well goitrogenic action TSH.