Stimulation by thyrotropin and cyclic AMP of the proliferation of quiescent canine thyroid cells cultured in a defined medium containing insulin

Roger, Pierre P.; Servais, Patricia; Dumont, Jacques Emile

doi:10.1016/0014-5793(83)80569-9

Cited by 145 publications

(75 citation statements)

References 39 publications

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“…Cells in Petri dishes were incubated for 48 h in the medium containing the indicated agent and, during the last 24 h, were incubated with 3 × 10 ¹5 mol/l thymidine, 10 ¹4 mol/l deoxycytidine (DOC), and 10 mCi/l [ 3 H]thymidine. After removal of the medium, the cells were fixed with methanol and extensively washed (17). Autoradiography was performed as described previously (17), directly in the Petri dishes.…”

Section: Cell Culture and Agentsmentioning

confidence: 99%

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Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells

Kimura¹,

Dumont²,

Fusco

et al. 1999

European Journal of Endocrinology

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In the rat thyroid cell lines PC Cl3, FRTL-5 and WRT, proliferation is mainly regulated by insulin or IGF, and TSH. However, the mechanism regulating cell mass doubling prior to division is still unknown. Our laboratory has shown that in dog thyroid cells insulin promotes growth in size while TSH in the presence of insulin triggers DNA replication. In the absence of insulin, TSH has no effect on cell growth. In this report we investigated insulin action on both cell mass and DNA synthesis and its modulation by TSH and insulin in PC Cl3 and FRTL-5 cells. In PC Cl3 cells, insulin activated not only DNA synthesis but also protein synthesis and accumulation. Although TSH potentiated the stimulation of DNA synthesis induced by insulin, enhancement of protein synthesis by both agents was additive. All TSH effects were reproduced by forskolin. Similar effects were also obtained in FRTL-5 cells. This suggests that insulin and TSH, via cAMP, modulate both growth in size and DNA replication in these cell lines.Lovastatin, which blocks 3-hydroxy-3-methylglutaryl coenzyme A reductase, decreased the induction of DNA synthesis, but not of protein synthesis induced by insulin or TSH in PC Cl3 cells. In FRTL-5 cells, lovastatin reduced protein and DNA synthesis stimulated by insulin but not TSH-induced protein synthesis. Taking these data together, we propose that insulin and/or TSH both modulate cell mass doubling and DNA synthesis in these cell lines, presumably via different pathways, and that there are at least two pathways which regulate growth in size in FRTL-5 thyroid cells: one triggered by insulin, which is lovastatin sensitive, and the other activated by TSH, which is not sensitive to lovastatin.

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Section: Cell Culture and Agentsmentioning

confidence: 99%

“…After removal of the medium, the cells were fixed with methanol and extensively washed (17). Autoradiography was performed as described previously (17), directly in the Petri dishes. The cells were stained with toluidine blue, and the proportion of labeled nuclei was determined by counting at least 1000 nuclei in each dish.…”

Section: Cell Culture and Agentsmentioning

confidence: 99%

Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells

Kimura¹,

Dumont²,

Fusco

et al. 1999

European Journal of Endocrinology

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“…Loss of this requirement is a classic feature of oncogenic transformation (Baserga et al, 1994). In various in vitro thyroid cell systems, including primary cultures of canine (Roger et al, 1983(Roger et al, , 1987a) and human thyrocytes (Roger et al, 1988;Williams et al, 1988), rat thyroid cell lines (Tramontano et al, 1988;Tominaga et al, 1994), as probably in adult human thyroid gland in vivo (Cheung et al, 1996), the main physiological regulator thyrotropin (TSH) acting through cyclic AMP (cAMP) , and IGF-1 or insulin synergistically stimulate DNA synthesis and cell proliferation. The mechanism(s) of this synergy is unclear.…”

Section: Introductionmentioning

confidence: 99%

Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture

et al. 1999

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The proliferation of most normal cells depends on the synergistic interaction of several growth factors and hormones, but the cell cycle basis for this combined requirement remains largely uncharacterized. We have addressed the question of the requirement for insulin/ IGF-1 also observed in many cell culture systems in the physiologically relevant system of primary cultures of dog thyroid epithelial cells stimulated by TSH, which exerts its mitogenic activity only via cAMP. The induction of cyclin A and cdc2, the phosphorylation of cdk2, the nuclear translocation of cdk4 and the assembly of cyclin D3-cdk4 complexes required the synergy of TSH and insulin. Cyclin D3 (the most abundant cyclin D) was necessary for the proliferation stimulated by TSH in the presence of insulin as shown by microinjection of a neutralizing antibody. Cyclin D3 accumulation and activity were dierentially regulated by insulin and TSH, which points out this cyclin as an integrator that ranks these comitogenic pathways as supportive and activatory, respectively. Paradoxically TSH alone strongly repressed cyclin D3 accumulation. This inhibition was overridden by insulin, which markedly stimulated cyclin D3 mRNA and protein accumulation, but failed to assemble cyclin D3-cdk4 complexes in the absence of TSH. TSH unmasked the DCS-22 epitope of cyclin D3 and assembled cyclin D3-cdk4 in the presence of insulin. These data demonstrate that cyclin D synthesis and cyclin D-cdk assembly can be dissociated and complementarily regulated by dierent agents and signalling pathways.

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“…For many fibroblast and established tumor cell lines, this second messenger is either without effect or is a negative regulator of proliferation (Pastan et al, 1975). In contrast, skin and mammary epithelia (Green, 1978;Yang et al, 1980), hepatocytes (Friedman et al, 1981), thyrocytes (Roger et al, 1983), Schwann cells (Raff et al, 1978a) and melanocytes (Mayer, 1982), among many other cell types, respond to elevation of intracellular cAMP by dividing. For these cells, combined application of cAMP and a polypeptide mitogen, such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) or insulin, typically promotes a synergistic (greater than additive) stimulation of cell proliferation (Raff et al, 1978a;McGowan et al, 1981;Roger and Dumont, 1984;Westermark et al, 1986;Roger et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

1990

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Stimulation by thyrotropin and cyclic AMP of the proliferation of quiescent canine thyroid cells cultured in a defined medium containing insulin

Cited by 145 publications

References 39 publications

Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells

Insulin and TSH promote growth in size of PC Cl3 rat thyroid cells, possibly via a pathway different from DNA synthesis: comparison with FRTL-5 cells

Cyclin D3 accumulation and activity integrate and rank the comitogenic pathways of thyrotropin and insulin in thyrocytes in primary culture

Cell-specific cyclic AMP-mediated induction of the PDGF receptor.

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