In the thyroid cells proliferation, differentiated and metabolic functions are under the control of different steps of the cyclic AMP cascade.
In the course of studies to elucidate the complex network of interactions controlling FRTL5 cell proliferation, thyroid stimulating hormone (TSH)-independent mutants (M cells), have been obtained from FRTL5 cells by chemical mutagenesis. In the present studies, the role of TSH on the proliferation and on differentiated and metabolic functions in these mutant cells have been investigated and compared to their response to insulin-like growth factor I (IGF-I). The addition of IGF-I to M cells leads to normal stimulation of DNA synthesis. However, inspite of the fact that mutant cells display normal TSH receptors, TSH is unable to stimulate the proliferation of the M cells. Nevertheless, TSH is able to increase intracellular levels of cAMP leading to regulation of TSH function in the M cells. On the other hand, TSH does not influence iodide transport and actin filaments depolimerization in these cells. However, aminoacid transport, stimulated in wild-type FRTL5 cells by both TSH and IGFs, is under the control of IGFs but not of TSH in the mutant cells. Neither TSH or IGF-I modified the expression of c-fos proto-oncogene in the M cells, probably because of high constitutive expression. These data suggest that a crucial signalling step(s) required for TSH induced mitogenesis is impaired in the M cells, and that this signalling step is not required for IGF-I induced mitogenesis.
Villone
G
G
Dpt. di Medicina Sperimentale e Clinica, Università degli Studi di Reggio Calabria, Catanzaro, Italy.
Veneziani
B M
BM
Picone
R
R
De Amicis
F
F
Perrotti
N
N
Tramontano
D
D
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004261:DNA Replication / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology
D000621:Aminoisobutyric Acids; D007454:Iodides; D016760:Proto-Oncogene Proteins c-fos; C100049:2-aminoisobutyric acid; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D000242:Cyclic AMP