Development of Regulatory Mechanisms in the Thyroid: Failure of Iodide to Suppress Iodide Transport Activity

Fetal, neonatal, and adult cat thyroid glands were investigated for their ability to respond to excess iodide in vitro with reduction in both iodide transport activity as measured by the 1251-T/M ratio and thyrotropin-stimulated cyclic AMP formation. Fetal and neonatal cat thyroids responded to thyrotropin addition with greater increases in cyclic AMP than those of adults. Moreover, in each group, pretreatment of the thyroid tissue with NaI (30 pmol for 2 hr) resulted in a significant reduction in the subsequent stimulation of cyclic AMP formation by thyrotropin. The 1251-T/M ratio in neonatal cat thyroid tissue was similar to that in adult animals of either sex, whereas the lz5I-T/M of fetal thyroid was greater than that of the mother. Moreover, while pretreatment of the thyroid tissue of neonatal or adult animals with excess iodide resulted in a reduction in iodide transport activity, no such reduction was observed in fetal thyroid tissue. These findings suggest that the autoregula- tory effect of iodide transport develops at a later gestational time than the action on thyrotropin-stimulated cyclic AMP formation. Exposure of thyroid tissue to high con- centrations (5-50 pA4) of iodide in vitro re- sults in a reduction in subsequently deter- mined iodide transport activity (1-3), as well as an inhibition of the stimulation of cyclic AMP formation induced by thyrotro- pin (TSH) or other thyroid stimulators (2, 4-9). These two actions of iodide on thyroid function are similar in that both are prevented by simultaneous treatment of the tissue with agents that inhibit intrathyroidal oxidative reactions, and both effects appear to occur through the mediation of as yet unidentified, iodide-containing inhibitory factors formed within the thyroid cell (1,4). There is no information available to indi- cate whether these two actions of iodide are mediated by the same or different iodide- containing inhibitory factors. The present study was undertaken to (a) ascertain whether these two actions of iodide can be observed in fetal or neonatal thyroid tissue and (b) to determine whether or not there is any difference in the fetal development of the thyroid responses to excess iodide. Material and Methods. A description of the animal groups employed in this study is presented in Table I. All animals were obtained from a local supplier (Quaker Farms, Quakertown, Pa.). They were housed in environmentally controlled rooms and allowed food and water ad libitum. In those groups utilizing newborn animals, the female was allowed to deliver normally and the date of delivery recorded during routine daily observation. Date of birth was taken as day zero. Pregnant and lactating groups were composed of animals donating the fetal and neonatal groups, re- spectively. Fetal and neonatal thyroids were obtained by careful dissection, weighed to the nearest 0.1 mg on a torsion bal- ance, and sectioned into eight pieces by dividing each lobe along its vertical and horizontal axis. Four thyroid sections, two from each lobe, were preincubated for 2 hr in 2.5 ml Eagle's minimum essential medium (10) supplemented with 30 pA4 NaI. The remaining sections were preincu- bated for 2 hr in the same medium without added iodide. Following the preincubation, the sections were subjected to two 30-min washes with Eagle's medium prior to the test incubation. This wash procedure has been shown previously to effectively re- move more than 90% of the added iodide (3). Finally, two thyroid sections from each preincubation group were taken for mea- surement of iodide transport activity and the remaining sections employed for the