title: Differential control of type-I iodothyronine deiodinase expression by the activation of the cyclic AMP and phosphoinositol signalling pathways in cultured human thyrocytes.
abstract: The effects of TSH and the activation of the cyclic AMP (cAMP) and Ca(2+)-phosphatidylinositol (Ca(2+)-PI) cascades on the activity and expression of the selenoenzyme thyroidal type-I iodothyronine deiodinase (ID-I) have been studied using human thyrocytes grown in primary culture. Stimulation of ID-I activity and expression was obtained with TSH and an analogue of cAMP, 8-bromo-cAMP. In the presence or absence of TSH, the addition of the phorbol ester, phorbol 12-myristate 13-acetate (PMA) together with the calcium ionophore A23187, caused a decrease in ID-I activity; a decrease in ID-I expression was also observed as assessed by cell labelling with [75Se]selenite. PMA alone had no effect on ID-I activity in the presence or absence of TSH. A23187 alone produced a small but significant reduction in ID-I activity, but only in TSH-stimulated cells. These data provide evidence that the expression of thyroidal ID-I is negatively regulated by the Ca(2+)-PI cascade, and positively regulated by the cAMP cascade.
authors.affiliation: University Department of Clinical Biochemistry, Royal Infirmary, Edinburgh, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Beech
authors.forename: S W
authors.initials: SW
authors.lastname: Walker
authors.forename: J R
authors.initials: JR
authors.lastname: Arthur
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.forename: G J
authors.initials: GJ
authors.lastname: Beckett
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002277:Carcinoma / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006111:Graves Disease / Q000473:pathology; D006801:Humans; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D008862:Microsomes, Liver / Q000378:metabolism; D010716:Phosphatidylinositols / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D051140:Selenoproteins; D015398:Signal Transduction / Q000187:drug effects*; D018038:Sodium Selenite / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology*; D013964:Thyroid Neoplasms / Q000473:pathology; D016606:Thyroid Nodule / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology*
chemical_list: D010716:Phosphatidylinositols; D011506:Proteins; D051140:Selenoproteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D013972:Thyrotropin; D000242:Cyclic AMP; D007453:Iodide Peroxidase; D018038:Sodium Selenite; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004121:Dimethyl Sulfoxide