Effects of epidermal growth factor on thyroglobulin and adenosine 3′, 5′-monophosphate production by cultured human thyrocytes

While several workers have identified epidermal growth factor (EGF) receptors on human thyroid membranes, very few reports have described EGF effects on intact human thyroid cells in primary culture, and these were short term studies indicating that EGF effects were primarily inhibitory [reduced iodide uptake and thyroglobulin (Tg), T₄, and T₃ release]. Paradoxically, in vivo EGF stimulates thyroid growth and increases colloid stores. In this study we examined the effects of EGF on cultured thyroid cells in regard to thymidine incorporation, Tg secretion, and cAMP production during a 12-day period. Addition of EGF (0–30 ng/mL) to medium for 6 or 12 days stimulated thymidine incorporation and enhanced Tg synthesis by thyroid cells. However, the profile of Tg release into medium was biphasic. Tg release was inhibited by EGF (0.1–10 ng/mL) during the first 3 days of culture, but the inhibitory effect disappeared by the sixth day, and EGF stimulated Tg release by day 12 and thereafter. EGF enhanced endogenous cAMP levels in thyroid cells, but did not augment TSH-stimulated increases in cAMP production. Our observations of EGFstimulated growth and inhibited Tg secretion during short term culture are consistent with the findings of earlier studies with nonhuman thyrocytes. However, the later phase of enhanced cAMP levels with stimulation of Tg secretion indicates that EGF may have trophic effects on thyrocytes previously unrecognized because of the short term nature of the studies. These observations suggest an important role for EGF in maintenance of normal thyroid physiology.