title: Age-related failure of endocytosis may be the pathogenetic mechanism responsible for "cold" follicle formation in the aging mouse thyroid.
abstract: With advancing age, 60-80% of the follicles of the mouse thyroid gland turn "cold", i.e. they lose their normal capacity to iodinate thyroglobulin (Tgb). Cold follicles are morphologically characterized by their large size, by deeply periodic acid-Schiff-stained colloid and by flat epithelial cells. We investigated the hypothesis that a progressive, age-related failure of endocytosis, leading to a gradually increasing mismatch between production of new Tgb and resorption of stored Tgb, could lead to overfilling of colloid stores with consecutive impediment of diffusion. To this purpose, labeling of the thyroids was started when mice were 3 months old, and 125I was continuously administered thereafter for 2-6 months. After this time, all follicles were homogeneously labeled in autoradiographs. Tracer application was then discontinued. Autoradiographs obtained at intervals during the washout of the tracer yielded a mirror image of that observed after acute labeling. The large follicles which were cold after acute labeling in old animals now still retained labeled iodoproteins even after 7 weeks of washout, i.e. at a time when morphologically normal follicles had long lost their labeled Tgb stores. Thus, the cold follicles of the old thyroid must have been functioning normally during equilibration of young thyroids, but have then gradually lost their capacity to iodinate and to remove stored Tgb from the colloid. The observation supports the thesis that aging primarily affects the cytoskeleton and, thus, the cell's endocytotic machinery. This effect of aging on the thyroid can be prevented by life-long stimulation of the gland by TSH.
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001345:Autoradiography; D002704:Chlorates / Q000494:pharmacology; D004705:Endocytosis; D005260:Female; D007455:Iodine / Q000008:administration & dosage; D007457:Iodine Radioisotopes; D008713:Methimazole / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D002704:Chlorates; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D008713:Methimazole; D013954:Thyroglobulin; D007455:Iodine; D013974:Thyroxine; C032706:sodium chlorate