Endocrine Abstracts

Tyrosine availability critically influences thyroid hormone synthesis, and thyroid disorders, such as hyperthyroidism, affect 1% of humans. In contrast, nearly 10% of mature/senior cats develop hyperthyroidism, but colourpoint breeds with mutations in the tyrosinase gene (e.g. Siamese) show reduced risk of developing hyperthyroidism, potentially due to increased availability of tyrosine (related to coat colouration). To establish how tyrosine availability can alter thyroid function, we used the well-established rat FRTL-5 thyroid cell line and investigated how manipulating tyrosine concentrations affected cell proliferation, gene expression and Thyroid Stimulating Hormone (TSH) responsiveness in vitro. FRTL-5 cells were grown in modified Coon’s F12 media with variable concentrations of tyrosine, phenylalanine or glycine, to create conditions of depleted, very low, moderate or high tyrosine conditions (range 0 to 140µM). Cell morphology remained consistent, regardless of tyrosine conditions. Furthermore, cell proliferation (as determined by crystal violet assays) was not significantly affected by tyrosine conditions. However, TSH-stimulated cell proliferation was dramatically inhibited in conditions of depleted, very low or moderate tyrosine. Increased phenylalanine availability did not compensate for the lack of tyrosine. These effects were reversible, upon return to tyrosine-replete conditions. Gene expression analyses (using multiplex RT-qPCR) revealed that tyrosine availability did not affect basal gene expression of any thyroid cell marker investigated, but the absence of tyrosine significantly inhibited TSH-stimulated Tg (thyroglobulin) and Tpo (thyroid peroxidase) expression, and significantly enhanced TSH-stimulated Slc26a4 (Pendrin) and Duox2 (Dual oxidase 2) expression. These data show that tyrosine availability can have direct effects on TSH-stimulated cell proliferation and gene expression in FRTL-5 thyroid cells, and reveals that genes associated with thyroid hormone synthesis (Tg, Tpo, Slc26a4, Duox2) are sensitive to tyrosine concentrations. If these changes are reflected in vivo in humans and cats, pharmacological or dietary manipulation of tyrosine availability could influence thyroid responsiveness and help prevent hyperthyroidism.