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Thyroglobulin (Tg) induces thyroid cell growth in a concentration-specific manner by a mechanism other than thyrotropin/cAMP stimulation
- Source :
- Biochemical and Biophysical Research Communications. 391:890-894
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- Thyroglobulin (Tg), a major product of the thyroid gland, serves as a macromolecular precursor of thyroid hormone biosynthesis. In addition, Tg stored in the thyroid follicles is a potent regulator of thyroid-specific gene expression. In conjunction with thyroid stimulating hormone (TSH) and iodide, Tg regulates thyroid follicle function, which is the minimal functional unit of the thyroid gland. In the present study, we show that Tg stimulates growth of FRTL-5 thyroid cells in the absence of TSH, insulin and serum. Unlike TSH, Tg did not increase cellular cyclic AMP (cAMP) levels; rather, the TSH signal counteracted Tg-induced cell growth. A specific inhibitor of A-kinase, H-89, did not modulate the effect of Tg. Tg increased kinase activity of Akt to the same level as TSH, insulin and 5% serum, while LY294002 abolished Tg-induced growth. Interestingly, low Tg concentrations maximized growth-promotion activity and induction of the apical iodide transporter (PDS; SLC26A4), whereas high Tg concentrations suppressed both cell growth and the expression of thyroid-specific genes. These results suggest that a low levels of Tg in the follicular lumen might stimulates cell growth and iodide transport to accelerate the iodide organification process; however, elevated Tg levels in the follicle might then shut down all of these functions.
- Subjects :
- endocrine system
medicine.medical_specialty
endocrine system diseases
medicine.medical_treatment
Thyroid Gland
Biophysics
Gene Expression
Thyrotropin
Thyroglobulin
Biochemistry
Cell Line
Thyroid hormone receptor beta
Thyroid-stimulating hormone
Thyroid peroxidase
Internal medicine
Cyclic AMP
medicine
Animals
Iodide transport
Molecular Biology
Cell Proliferation
Thyroid hormone receptor
biology
Chemistry
Thyroid
Cell Biology
Organification
Cyclic AMP-Dependent Protein Kinases
Rats
medicine.anatomical_structure
Endocrinology
biology.protein
Thymidine
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 391
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....1c03549352ea7d794b975892f61a6b54