In vitro demonstration of a TSH-specific growth desensitising mechanism in rat thyroid epithelium

Sustained elevation of serum thyrotropin (TSH) induces an initial proliferation of rat thyroid follicular cells, leading to goitre formation followed by a 'plateau phase' in which the growth response to TSH is lost. To investigate this growth desensitisation mechanism, we have compared the sensitivity to growth factors of normal and 'plateau phase' rat thyroid epithelium in primary follicle cultures. Insulin at supraphysiological concentrations stimulates growth (DNA synthesis) in both cell types. TSH at a concentration found in 'plateau phase' animals (0.1 mU/ml) is maximally growth stimulatory for normal, but not significantly stimulatory for 'plateau' epithelium. At much higher concentrations however (greater than or equal to mU/ml) an equal response is obtained from both. We conclude that the growth desensitising mechanism is intrinsic to the follicular cell, is at least partly specific to TSH, and is effective only over the range of TSH concentrations found in vivo.