Ultrastructural and functional alterations of the rat thyroid gland produced by polychlorinated biphenyls compared with iodide excess and deficiency, and thyrotropin and thyroxine administration

Summary

Histologic and ultrastructural lesions in thyroid follicular cells of Osborne-Mendel rats produced by feeding diets containing 5, 50, and 500 ppm polychlorinated biphenyls (PCB) for 4 weeks were compared with alterations produced by low (Remington diet) and high (1%KI) iodide diets, chronic thyroxine administration, and a single injection of thyrotropin.

Exposure to PCB resulted in a dose-dependent hypertrophy and hyperplasia of follicular cells with an abnormal accumulation of large colloid droplets and irregular lysosomes. There was limited evidence of colloid droplet-lysosome interaction necessary for the secretion of thyroid hormones. Microvilli on luminal surfaces were decreased, abnormally shaped, and short. Serum thyroxine and triiodothyronine were decreased significantly after feeding PCB.

Follicular cells in rats fed the iodine-deficient diet underwent hypertrophy and hyperplasia with increased development of rough endoplasmic reticulum. They had increased numbers of round lysosomes and colloid droplets. There were numerous uniformly long microvilli and occasional pseudopodia were present engulfing colloid. Serum thyroxine was significantly decreased but triiodothyronine levels were increased. The iodide-excess diet resulted in hypertrophy and hyperplasia of follicular cells which contained numerous colloid droplets and abnormally shaped lysosomes with little evidence of fusion. Numerous long microvilli extended into the lumen. Many follicular cells contained unique intracytoplasmic microfollicles lined by uniform microvilli. Serum thyroxine was significantly reduced.

Follicular cells of rats chronically administered thyroxine underwent involution and had only a few short microvilli, scattered round lysosomes, and poorly developed organelles. Serum thyroxine and triiodothyronine were elevated significantly. Thyrotropin (TSH) produced hypertrophy of follicular cells by 30 min post-injection with increased large colloid droplets and small round lysosomes. Large pseudopod-like projections of follicular cells were involved in endocytosis of colloid. There was evidence of fusion of lysosomal membranes with colloid droplets. Circulating thyroid hormone levels were significantly elevated from 30 min to 8 h after administration of thyrotropin but normal by 24 h.

The ultrastructural alterations produced by PCB in the luminal plasma membrane and structure of microvilli were distinct from changes observed with acute stimulation by TSH, long-term stimulation by iodide excess or deficient diets, and chronic suppression by thyroxine. The changes in lysosomal structure and the accumulation of colloid droplets with little evidence of fusion in follicular cells of rats fed PCB closely resembled the findings in rats fed the iodide-excess diet. The principal effect of PCB on follicular cells appeared to be on limiting colloid droplet-lysosome interaction thereby inhibiting the proteolysis of thyroglobulin necessary for the release of thyroid hormones.