title: Thyroglobulin (Tg) induces thyroid cell growth in a concentration-specific manner by a mechanism other than thyrotropin/cAMP stimulation.
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.
authors: Department of Internal Medicine, Ito Hospital, Tokyo 150-8308, Japan.
authors: Yoshihiko
authors: Y
authors: Noguchi
authors: Norikazu
authors: N
authors: Harii
authors: Cesidio
authors: C
authors: Giuliani
authors: Ichiro
authors: I
authors: Tatsuno
authors: Koichi
authors: K
authors: Suzuki
authors: Leonard D
authors: LD
authors: Kohn
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013954:Thyroglobulin / Q000378:metabolism* / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013972:Thyrotropin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D013972:Thyrotropin; D013954:Thyroglobulin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D013936:Thymidine