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G protein-linked receptors in the thyroid
D Corda1, C Bizzarri, M Di Girolamo
1Istituto di Richerche Biomediche e Farmacologiche, Mario Negri, Consorzio Mario Negri Sud, Chieti, Italy.
Abstract:
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.
Insights
FRTL5 cells reveal complex thyroid signaling pathways. Thyroid-stimulating hormone (TSH) and adrenergic stimulation activate distinct second messenger systems for iodide transport and cell growth regulation.
Area of Science:
- Thyroid cell biology
- Endocrinology
- Molecular signaling
Background:
- The FRTL5 cell line is a valuable model for studying thyroid function.
- These cells possess multiple receptors (TSH, adrenergic, muscarinic, insulin, IGF1) linked to signal transduction pathways.
Purpose of the Study:
- To investigate the distinct intracellular signaling mechanisms underlying thyroid hormone regulation in FRTL5 cells.
- To explore the interactions between various second messengers in response to hormonal stimulation.
Main Methods:
- Utilized the FRTL5 cell line to analyze hormonal activation and thyroid function.
- Investigated receptor-mediated signaling pathways and second messenger interactions (Ca++, arachidonic acid, adenylyl cyclase).
Main Results:
- Adrenergic stimulation of iodide efflux involves calcium and arachidonic acid.
- Thyroid-stimulating hormone (TSH) regulates iodide transport through potentially different signaling pathways.
- TSH also influences cell growth via adenylyl cyclase and may modulate an endogenous ADP-ribosyl transferase.
Conclusions:
- FRTL5 cells provide a model to dissect complex thyroid signaling.
- Distinct second messenger systems mediate responses to TSH and adrenergic agonists.
- The role of TSH-induced ADP-ribosyl transferase activity in thyroid physiology requires further investigation.