Increases in cytosolic Ca++ down regulate thyrotropin receptor gene expression by a mechanism different from the cAMP signal.
Thyrotropin (TSH) receptor mRNA levels in rat FRTL-5 thyroid cells are decreased by treatment with the calcium ionophores, A23187 or ionomycin, as well as with TSH, cholera toxin, forskolin, and 8-bromo-cAMP. Down regulation is, in each case, associated with a decrease in [125I]TSH binding and a decreased ability of TSH to increase cAMP levels. The ionophore does not alter cAMP levels and ethylene glycol-bis-(beta-aminoethyl ether) N, N'-tetraacetic acid (EGTA) in the medium prevents down regulation of TSH receptor mRNA levels by the ionophore, but not by TSH; the EGTA action is reversed by the simultaneous addition of Ca++. Whereas down regulation by TSH and its cAMP signal requires the presence of insulin and/or serum in the medium; down regulation by a calcium ionophore is still evident in their absence. Down regulation of TSH receptor mRNA levels and receptor desensitization by TSH/cAMP or an ionophore is lost in cells transfected with a full length TSH receptor cDNA devoid of regulatory elements, but able to reconstitute TSH receptor signal generation.
Saji
M
M
Section on Cell Regulation, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, MD 20892.
Ikuyama
S
S
Akamizu
T
T
Kohn
L D
LD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003600:Cytosol / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011989:Receptors, Thyrotropin / Q000187:drug effects / Q000235:genetics*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013961:Thyroid Gland; D014162:Transfection
D002147:Calmodulin; D011989:Receptors, Thyrotropin; D013449:Sulfonamides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004533:Egtazic Acid; D015759:Ionomycin; D012313:RNA; C017967:W 7; D002772:Cholera Toxin; D004492:Edetic Acid; D000242:Cyclic AMP; D002118:Calcium