Enhancement of thyrotropin-stimulated iodide organification in porcine thyroid cells after protein kinase-C inhibition.
We and others have previously shown that 12-O-tetracanoylphorbol-13-acetate (TPA), a protein kinase-C (PKC) activator, inhibits TSH-stimulated iodide organification in porcine thyroid cells. However, TPA action may be independent of PKC. To further explore the role of PKC in the regulation of differentiated thyroid function, we studied the effects of the PKC inhibitors 1-O-hexadecyl-2-O-methylglycerol (AMG-C16), 1-(5-isoquinolinesulfonyl)2-methylpiperazine (H7), and staurosporine on TSH-stimulated iodide organification in porcine thyroid cells in the presence and absence of TPA. AMG-C16 increased basal iodide organification in concentrations ranging from 15-240 microM (P < 0.01, by analysis of variance). Such stimulation by AMG-C16 (30-120 microM) persisted in the presence of submaximal (10 microU) and maximal (1 mU) concentrations of TSH. However, in the presence of TPA (> 10 nM), the effects of AMG-C16 were abolished. H7 (50 microM) and staurosporine (100 nM) also enhanced TSH-stimulated iodide organification. In the presence of staurosporine and TPA, no inhibition of TSH-stimulated iodide organification was observed. However, H7 could not reverse the effects of TPA. In summary, these studies indicate that in porcine thyroid cells, three distinct PKC inhibitors all enhanced TSH-stimulated iodide organification and that staurosporine reversed the effects of TPA on TSH-stimulated iodide organification. These findings are consistent with the concept that PKC acts as an endogenous negative modulator of iodide organification in vitro.
Ginsberg
J
J
Department of Medicine, University of Alberta, Edmonton, Canada.
Matowe
W
W
Murray
P G
PG
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005995:Glyceryl Ethers / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D019311:Staurosporine; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D000470:Alkaloids; D005995:Glyceryl Ethers; D007454:Iodides; D007546:Isoquinolines; D010879:Piperazines; C059039:1-O-hexadecyl-2-O-methylglycerol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013972:Thyrotropin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate