TY - JOUR
T1 - Thyroid-stimulating hormone and insulin-like growth factor-1 synergize to elevate 1,2-diacylglycerol in rat thyroid cells. Stimulation of DNA synthesis via interaction between lipid and adenylyl cyclase signal transduction systems
AU - Brenner-Gati, L.
AU - Berg, K. A.
AU - Gershengorn, M. C.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1988
Y1 - 1988
N2 - Thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) synergistically stimulate DNA synthesis in thyroid cells. In this report, a novel mechanism for mediation of this synergistic interaction is described in rat thyroid (FRTL-5) cells. Because phorbol myristate acetate stimulates DNA synthesis, the effects of TSH, IGF-1 and insulin on FRTL-5 cell content of 1,2-diacylglycerol (1,2-DG), the endogenous activator of protein kinase C, were measured. After 6 d, TSH, IGF-1 and insulin caused increases in cellular 1,2-DG (mean ± SE) to 180 ± 10%, 540 ± 50%, and 360 ± 40% of control, respectively, whereas TSH plus IGF-1 and TSH plus insulin synergistically increased 1,2-DG to 1,890 ± 310% and 1,690 ± 230%, respectively. In the absence of insulin, the efefect of TSH to elevate 1,2-DG exhibited an EC50 of ~ 2,000 μU/ml. The synergistic interaction of insulin and TSH was found to increase the potency of TSH by 300-fold (EC50 was ~ 7 μU/ml) in addition to increasing the efficacy of TSH. The effect of TSH appeared to be mediated by TSH-stimulated increases in cyclic AMP (cAMP). Forskolin and 8-bromo-cAMP, like TSH, caused modest increases in 1,2-DG and DNA synthesis, whereas forskolin plus insulin and 8-bromo-cAMP plus insulin markedly elevated 1,2-DG content and stimulated DNA synthesis. Under all conditions, increases in 1,2-DG content correlated with stimulation of DNA synthesis. These findings suggest that the synergistic stimulation of DNA synthesis in thyroid cells by TSH, via cAMP, and IGF-1 is mediated by 1,2-DG. Moreover, they implicate a novel interaction between the lipid and adenylyl cyclase signaling systems for the regulation of cell proliferation.
AB - Thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) synergistically stimulate DNA synthesis in thyroid cells. In this report, a novel mechanism for mediation of this synergistic interaction is described in rat thyroid (FRTL-5) cells. Because phorbol myristate acetate stimulates DNA synthesis, the effects of TSH, IGF-1 and insulin on FRTL-5 cell content of 1,2-diacylglycerol (1,2-DG), the endogenous activator of protein kinase C, were measured. After 6 d, TSH, IGF-1 and insulin caused increases in cellular 1,2-DG (mean ± SE) to 180 ± 10%, 540 ± 50%, and 360 ± 40% of control, respectively, whereas TSH plus IGF-1 and TSH plus insulin synergistically increased 1,2-DG to 1,890 ± 310% and 1,690 ± 230%, respectively. In the absence of insulin, the efefect of TSH to elevate 1,2-DG exhibited an EC50 of ~ 2,000 μU/ml. The synergistic interaction of insulin and TSH was found to increase the potency of TSH by 300-fold (EC50 was ~ 7 μU/ml) in addition to increasing the efficacy of TSH. The effect of TSH appeared to be mediated by TSH-stimulated increases in cyclic AMP (cAMP). Forskolin and 8-bromo-cAMP, like TSH, caused modest increases in 1,2-DG and DNA synthesis, whereas forskolin plus insulin and 8-bromo-cAMP plus insulin markedly elevated 1,2-DG content and stimulated DNA synthesis. Under all conditions, increases in 1,2-DG content correlated with stimulation of DNA synthesis. These findings suggest that the synergistic stimulation of DNA synthesis in thyroid cells by TSH, via cAMP, and IGF-1 is mediated by 1,2-DG. Moreover, they implicate a novel interaction between the lipid and adenylyl cyclase signaling systems for the regulation of cell proliferation.
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U2 - 10.1172/JCI113672
DO - 10.1172/JCI113672
M3 - Article
C2 - 2843569
AN - SCOPUS:0023773065
VL - 82
SP - 1144
EP - 1148
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -