title: Human fetal thyroid cell growth in vitro: system characterization and cytokine inhibition.
abstract: We have studied primary human fetal thyroid cell monolayers as an in vitro model for thyroid cell growth and function. Fetal thyroid cells grew slowly in a serum-free medium under basal conditions (i.e. without insulin and TSH), with a doubling time of 112 +/- 7 h (mean +/- SEM), indicating autonomous growth capacity. Addition of insulin (10 micrograms/ml) lead to increased growth, with a doubling time of 43.0 +/- 2.5 h, and TSH further reduced the doubling time in a dose-dependent manner, with the highest growth rate at 1-10 mU/ml (doubling time, 27 +/- 0.5 h). These growth rates were only observed when cells were subjected to a short culture time (12 h) before investigation, whereas after 96 h of culture the fetal thyroid cell growth rate was reduced by up to 50%. Addition of more than 5% serum completely inhibited the growth stimulation initiated by insulin and TSH. The accumulation of extracellular cAMP by the fetal cell monolayer was induced by TSH in a dose-dependent manner and reached a maximum effect at 10 mU/ml (4.8 +/- 0.6 pmol cAMP). Basal thyroglobulin (Tg) release was 26.9 +/- 0.5 ng/10(5) cells.day. Insulin decreased Tg release to 16.7 +/- 0.5 ng/10(5) cells,day, whereas TSH increased it up to 52.5 +/- 1.0 ng/10(5) cells.day. The T cell cytokine gamma-interferon, a product of the lymphocytic infiltrate in autoimmune thyroid disease, significantly reduced both insulin and TSH-stimulated cellular growth as well as accumulation of Tg. In conclusion, human fetal thyroid cell monolayers grew at high velocity under defined experimental conditions in vitro. These conditions included a low serum concentration, short culture time before investigation, and insulin/TSH supplementation. Furthermore, this human thyroid model confirms our earlier observations on the influence of cytokines in thyroid cell growth regulation.
authors: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors: G K
authors: GK
authors: Huber
authors: T F
authors: TF
authors: Davies
mesh_terms: D001769:Blood; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D013972:Thyrotropin / Q000494:pharmacology
chemical_list: D007328:Insulin; D007371:Interferon-gamma; D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP