G protein-linked receptors in the thyroid.
The FRTL5 cell line has the advantage that its hormonal activation leads to important and measurable thyroid function such as the transport of iodide and the iodination of thyroglobulin. Secondly, the coexistence in the plasma membrane of these cells of several physiologically relevant receptors (TSH, alpha 1-adrenergic, M1 and M2 muscarinic, insulin, IGF1) coupled to at least three transducing enzymes (adenylyl cyclase, PLC, PLA2) gives the possibility to analyze the interaction among second messengers in the cell activation process. This has allowed us and others to show that in the case of the iodide efflux regulation at least two second messengers (Ca++ and arachidonic acid) mediate the adrenergic stimulation, whereas the TSH activation of the same phenomenon probably uses other signals in addition to Ca++ and arachidonic acid. Growth is mostly regulated by TSH, that activates the adenylyl cyclase by a mechanism that may involve the modulation of the availability of Gi. TSH is also able to regulate an endogenous ADP ribosyl transferase in FRTL5. This could be a novel mechanism of cell regulation by this hormone, but the role of this phenomenon in the physiological action of TSH is still unclear.
Corda
D
D
Istituto di Richerche Biomediche e Farmacologiche, Mario Negri, Consorzio Mario Negri Sud, Chieti, Italy.
Bizzarri
C
C
Di Girolamo
M
M
Valitutti
S
S
Luini
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006160:Guanosine Triphosphate / Q000502:physiology; D010740:Phospholipases / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000502:physiology
D001095:Arachidonic Acids; D011956:Receptors, Cell Surface; D016718:Arachidonic Acid; D006160:Guanosine Triphosphate; D013972:Thyrotropin; D010740:Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D002118:Calcium