Regulation of Thyroid Follicular Volume by Bidirectional Transepithelial Ion-Transport

Previous studies have shown that thyroid cells in monolayer culture exhibit bidirectional ion transport comprising apical-to-basal amiloride-sensitive Na+ transport and oppositely directed bumetanide-sensitive Cl- transport. We have now investigated the role of ion transport in the regulation of thyroid follicular size using follicular primary porcine thyroid cell cultures. Bumetanide (10-mu-M) added at the beginning of culture inhibited the formation of follicular lumina and caused a fall in follicle height when added to 3-day-old cultures. In contrast, phenamil (1-mu-M; an amiloride analog) increased follicle size both in freshly isolated and 3-day-old cultures. The effect of bumetanide was prevented by the prior addition of phenamil. Micropuncture studies showed that follicles had a lumen-negative, basal-positive transepithelial potential difference which was progressively reduced in magnitude by the serial addition of bumetanide (10-mu-M) and phenamil (1-mu-M). We conclude that thyroid follicles possess a bidirectional ion transport system which transports Na+ in an apical-to-basal direction and Cl- in the opposite direction. The balance between these two processes determines net solute flux and hence follicular size. A physiological role of ion transport in the thyroid may be to regulate follicular volume suggesting that abnormalities of ion transport may be responsible for disorders of follicular size