Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane

Abstract

II, Ekholm R, Ericson LE. Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane. Acta Endocrinol 1992:126: 67-74.ISSN 0001-5 598The intracellular regulation of thyrotropin-stimulated iodide efflux was studied in polarized porcine thyrocytes grown as a continuous, tight monolayer in bicameral culture chambers. From a previous study using this system we know that thyrotropin rapidly increases iodide efflux in the apical but not basal direction of the polarized epithelium.[125I]-iodide efflux in apical direction was stimulated by thyrotropin in a concentration-dependent manner (1\p=n-\10 U/I), whereas efflux in basal direction was unchanged at any thyrotropin dose. Thyrotropin-induced elevation of intracellular cAMP showed a corresponding concentration dependence. The selective stimulation of apical efflux by thyrotropin was evident also when re-uptake of iodide released in basal direction was blocked by perchlorate. The effect of thyrotropin on apical efflux was mimicked by 8-bromo-cAMP and forskolin, whereas agents known to activate the Ca2 + /phosphatidylinositol cascade (epidermal growth factor) and protein kinase C (phorbol ester) or increase cytosolic [Ca2 + ] (A23187) were inactive. We conclude that the selective stimulation by thyrotropin of apical iodide efflux, corresponding to efflux in luminal direction in intact follicles, occurs via cAMP-regulated iodide channels present in the apical domain of the plasma membrane.The ability of the thyroid to concentrate iodide is essential for the proper synthesis of thyroid hormones. Many studies have detailed the mechanism by which the thyroid follicle cell (thyrocyte) takes up iodide from the tissue interstitium. This process, taking place at the basolateral domain of the plasma membrane (1), is stimulated by TSH; as the stimulation is blocked by inhibitors of protein synthesis (2-4), it probably involves new iodide carrier molecules. Another component in iodide transport is iodide efflux from the thyrocytes. As originally found in vivo in the rat (5) and later demonstrated in vitro in thyroid lobes (6) and slices (7), TSH stimulates, with a delay of several hours, the disappearance from the gland of previously trapped iodide. This transport is obviously directed from the follicle lumen to the interstitium, across the epithelium; provided that the transport is transcellular (and not paracellular) the efflux observed in intact follicles must occur across the basolateral plasma membrane of the epithelial cells. TSH-stimulated iodide efflux has also been recognized in dispersed thyrocytes and thyrocytes in culture (2,3,(8)(9)(10)(11)(12). In these studies, however, iodide efflux was stimulated within a few minutes of exposure to TSH. It appears, therefore, that the TSH-stimulated iodide efflux observed in isolated thyrocytes is funda¬ mentally different from the efflux observed in thyroid tissue with intact follicular arrangement.In recent years, increased attention has been paid to the intracellular...

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

“…Yet, these experiments do not completely exclude a possible role of pendrin or of other channels in iodide efflux under basal conditions in these and other species. As a matter of fact, the relative role of these membrane proteins may vary between species as does the second messenger at play during TSH stimulation: cAMP increases iodide release from pig thyroid cells in primary cultures (24,28) while increase in intracellular Ca 2ϩ plays the prominent role in PCCl3 and FRTL-5 rat thyroid cells as shown here and in dog and human thyroid. Many such biochemical interspecies differences have been observed among mammalian thyroids (19,35).…”

Functional Characterization of Pendrin in a Polarized Cell System

“…In the latter system, bidirectional measurements indicate that thyrotropin stimulates iodide efflux in apical direction, leaving efflux in the basal direction unchanged, thus facilitating vectorial transport of iodide into the follicular lumen (43). The expression of NIS and pendrin in the heterologous polarized system used in this study will permit further characterization of the regulation and kinetics of pendrin-mediated iodide efflux.…”

“…Thyrotropin rapidly stimulates iodide efflux in FRTL-5 cells, which lack a distinct polarity, and in polarized porcine thyrocytes (42)(43)(44). In the latter system, bidirectional measurements indicate that thyrotropin stimulates iodide efflux in apical direction, leaving efflux in the basal direction unchanged, thus facilitating vectorial transport of iodide into the follicular lumen (43).…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…A number of cell models and setups are available to study NIS-mediated iodide transport (4)(5)(6)31,33,(39)(40)(41), including multiple heterologous cell lines transiently expressing NIS (29,42). Such studies are useful for the characterization of NIS function and the activities of naturally occurring or artificial mutant proteins (29,42).…”