Stimulation of thyrocytes with thyroid stimulating hormone (TSH) leads to a morphological change and a massive increase in thyroglobulin (Tg) production. Although Tg is a demanding client of the endoplasmic reticulum (ER), its increase did not result in significant accumulation of unfolded protein in the ER. Instead, ER chaperones and folding enzymes reached maximum synthesis rates immediately after TSH stimulation, before significant upregulation of Tg synthesis. The resulting increase in folding capacity before client protein production prevented cellular unfolded-protein stress, confirmed by the silence of the most conserved branch of the unfolded protein response. Thyrocytes set an example of physiological adaptation of cells to a future potentially stress-causing situation, which suggests a general strategy for both non-secretory and specialized secretory cells.