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Hormonogenesis in thyroid cells cultured on porous bottom chambers
Insights
This study used a novel cell culture system to investigate thyroid hormone production. The results show that thyroid-stimulating hormone (TSH) is crucial for hormone synthesis and iodide uptake, while high iodide levels can inhibit these processes.
Area of Science:
- Endocrinology
- Cell Biology
- Thyroid Physiology
Background:
- Thyroid hormonogenesis involves complex processes including thyroglobulin synthesis, thyroperoxidase activity, and hydrogen peroxide generation.
- Regulation of these processes by thyroid-stimulating hormone (TSH) and iodide is critical for thyroid hormone production.
- Understanding these mechanisms is essential for diagnosing and treating thyroid disorders.
Purpose of the Study:
- To investigate the polarized secretion and regulation of thyroid hormonogenesis using porcine thyroid cells in a specialized culture system.
- To elucidate the role of TSH and iodide in key steps of thyroid hormone synthesis.
- To evaluate the utility of this culture system for pharmacological and toxicological studies.
Main Methods:
- Culturing porcine thyroid cells in porous bottomed chambers to create a polarized monolayer.
- Independently accessing apical and basolateral cell poles for controlled media application.
- Measuring thyroglobulin secretion, synthesis, mRNA levels, iodide transport, iodination, and hormonogenesis efficiency.
Main Results:
- TSH significantly increased thyroglobulin synthesis, secretion, and mRNA levels, mediated by adenylcyclase stimulation.
- Active iodide transport, iodination, and hormonogenesis occurred only in the presence of TSH, primarily at the apical cell pole.
- High iodide concentrations (>0.5 microM) and certain media components (vitamins, amino acids, phenol red) inhibited iodination and hormonogenesis.
Conclusions:
- The developed culture system effectively reproduces thyroid cell functional bipolarity and allows independent manipulation of apical and basolateral environments.
- TSH is essential for thyroid hormone synthesis, regulating iodide uptake and thyroglobulin iodination.
- This model system is valuable for studying thyroid function and identifying potential inhibitors of thyroid hormonogenesis.
Abstract:
Different processes implied in thyroid hormonogenesis (thyroglobulin, thyroperoxidase and hydrogen peroxide generating system expressions) and their regulation by TSH and iodide have been studied using porcine thyroid cells cultured in porous bottomed chambers. This system allowed to reproduce the functional bipolarity. Cells form a tight and polarized monolayer. Both apical and basolateral poles of epithelial cells were independently accessible and the cell layer separated two compartments which can contain different media. A major polarized secretion of thyroglobulin into the apical compartment was observed; it was increased in the presence of TSH as well as the thyroglobulin synthesis and mRNA level. These TSH effects were the consequence of adenylcyclase stimulation. Active transport of iodide, iodination of thyroglobulin and hormonosynthesis took place only in the presence of TSH. These steps occurred at the apical pole of cells. In the culture chamber system, thyroglobulin was weakly iodinated (6 atoms of iodide per mole of thyroglobulin; in vivo up to 40 atoms per mole) but hormonogenesis efficiency was close to this one observed in vivo (40%). Iodide concentrations higher than 0.5 microM daily added to the basal medium inhibited iodination of thyroglobulin and hormonosynthesis. Some components contained in culture media were inhibitors for iodination when they were present in the apical medium such as vitamins, amino acids and phenol red. The culture system appears to be interesting for pharmacological and toxicological studies.