갑상선 세포의 성장에 대한 TSH 및 IGF-I의 신호전달과정에서 백일해독소 예민성 G-단백의 역할

Abstract

To evaluate the effect of pertussis toxin sensitive G-proteins on the growth of thyrocytes by TSH and IGF-I, we measured 3H-thymidine incorporation into FRTL-5 cells stimulated by TSH and/or IGF-I. Thymidine incorporation into FRTL-5 cells by TSH(1 mU/ml) or IGF-I (10 ng/ml) was significantly inhibited by the pretreatment of pertussis toxin (25 ug/ml). Adenosine (1mM) inhibited both TSH-and IGF-I- stimulated thymidine incorporation into FRTL-5 cells and the synergistic effect of TSH and IGF-I. This inhibitory effect of adenosine on TSH-or 1GF-I-stimulated thymidine incorporation was blocked partially by the pretreatment of pertussis toxin. However, the inhibition of the synergism of TSH and IGF-I by adenosine was not altered by the pretreatment of pertussis toxin. Indomethacin (100 uM) inhibited TSH effects by 60% and inhibieed IGF-1 effects by 5096 at 24 hours of incubation and then enhanced IGF-I effects in the prolonged incubation. Indomethacin blunted the synergism of TSH and IGF-I. These inhibitory effects of indomethacin were altered by the pretreatment of pertussis toxin. The pretreatment of pertussis toxin did not affect the inhibitory effect of indomethacin on the synergism of TSH and IGF-I at 24 hours of incubation. However, in the prolonged incubation (72 hours) the pretreatment of pertussis toxin significantly blocked the indomethacin effect. These findings suggest that pertussis toxin-sensitive G-proteins are involved in the signal transduction of TSH and/or IGF-1-stimulated growth of FRTL-5 cells and arachidonate metabolites should be involved in the mediation of synergism of growth stimulation induced by TSH and IGF-l in FRTL-5 cells.