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Thyroid hormone export varies among primary cells and appears to differ from hormone uptake
Francisco A R Neves1, Ralph R Cavalieri, Luiz A Simeoni
1Department of Pharmaceutical Sciences, University of Brasília, Brasília, DF 70910-900, Brazil.
Endocrinology
|January 18, 2002
Summary
Thyroid hormone (T3) efflux varies significantly across human placenta, cardiac, and kidney cells. Verapamil and other iodothyronines differentially affect T3 transport, indicating tissue-specific mechanisms regulate thyroid hormone action.
Area of Science:
- Endocrinology
- Cell Biology
- Pharmacology
Background:
- Thyroid hormone (T3) action is regulated by cellular uptake and efflux mechanisms.
- Understanding tissue-specific transport is crucial for comprehending thyroid hormone bioavailability and action.
Purpose of the Study:
- To characterize the efflux of T3 in primary cell cultures from human placenta, neonatal rat cardiac myocytes, and rat inner medullary collecting ducts (IMCD).
- To investigate the role of verapamil and unlabeled iodothyronines in modulating T3 efflux.
- To determine if T3 uptake and efflux mechanisms are distinct and tissue-specific.
Main Methods:
- Primary cell cultures of human placenta, neonatal rat cardiac myocytes, and rat IMCD cells were used.
- [125I]T3 efflux was measured in the presence and absence of verapamil and unlabeled iodothyronines.
- Differential inhibition of [125I]T3 efflux and uptake by various compounds was analyzed.
Main Results:
- T3 efflux rates were highest in placenta cells, followed by cardiac myocytes (ventriculocytes, atriocytes), and IMCD cells.
- Verapamil inhibited [125I]T3 efflux in a dose-dependent manner, with greater effect in placenta cells.
- Unlabeled iodothyronines and D-T3 showed differential inhibition patterns, suggesting distinct transporters for T3 efflux in different cell types.
- TRIAC inhibited T3 uptake but not efflux, indicating separate transport systems.
Conclusions:
- Significant differences in T3 efflux exist across various cell types, including placenta, cardiac, and renal cells.
- Verapamil and iodothyronine structure influence T3 efflux, highlighting the presence of specific transport proteins.
- Distinct carrier/transporter proteins mediate T3 uptake and efflux, with tissue-specific variations.
- Differential thyroid hormone transport in target cells is a key mechanism for regulating tissue-specific hormone action.