General inhibition by transforming growth factor beta 1 of thyrotropin and cAMP responses in human thyroid cells in primary culture.
Transforming growth factor beta 1 (TGF beta 1) mRNA has previously been identified in human thyroid cells and this agent has been shown to inhibit DNA synthesis in thyroid cells of some other species. In normal human thyroid cells in primary culture, TGF beta 1 inhibited inconstantly the low basal DNA synthesis and strongly the stimulation of DNA synthesis by epidermal growth factor (EGF) and serum, and by thyroid-stimulating hormone (TSH) acting through cAMP. This inhibition, by TGF beta 1, of the TSH and cAMP-dependent DNA synthesis was associated with an inhibition of PCNA (proliferating cell nuclear antigen) synthesis. TGF beta 1 almost completely abolished the cAMP induced stimulation of iodide uptake and thyroperoxidase synthesis. It thus, like EGF, also acts as a dedifferentiating agent. Investigation of the pattern of protein synthesis by two-dimensional gel electrophoresis revealed that while TGF beta 1, by itself, increased the synthesis of only one protein, a tropomyosin isoform, it inhibited most of the effects of cAMP on protein synthesis (35 out of 45 cAMP-regulated proteins were affected). It also reversed the effect of cAMP on the morphology of the thyrocytes. The fact that TGF beta 1 did not affect the increase in cAMP provoked by TSH in human thyroid cells while inhibiting most of the effects of dibutyryl cAMP in these cells suggests an action at a step distal to cAMP generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Taton
M
M
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Lamy
F
F
Roger
P P
PP
Dumont
J E
JE
D001790:Blood Physiological Phenomena; D003994:Bucladesine / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D003864:Depression, Chemical; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007454:Iodides / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects*; D013972:Thyrotropin / Q000037:antagonists & inhibitors*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007454:Iodides; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011500:Protein Synthesis Inhibitors; D016212:Transforming Growth Factor beta; D005576:Colforsin; D004815:Epidermal Growth Factor; D003994:Bucladesine; D013972:Thyrotropin