Ultrastructural and functional effects of chronic endogenous stimulation of thyroid cells by thyrotropin

Following total thyroidectomy, a small quantity of thyroid tissue was transplanted to the spleen in order to study thyroid tissue subjected to chronically elevated levels of endogenous thyrotropin (TSH). Plasma thyroxine (T4) and TSH levels were monitored and correlated with ultrastructural studies of the tissue over a 32-week experimental period. The effects of administration of an iodine-poor diet, and exogenous acute dose of TSH, and suppression of endogenous TSH through thyroxine administration were studied in order to evaluate the plasticity of the experimental model. Plasma T4 decreased after the first week and remained at approximately one half of the initial value until 12 weeks. Plasma TSH increased to a high of 6,220 ng/ ml after 6 weeks and gradually declined to one half of that value. The transplanted tissue remained functional throughout the experimental period. The number of pseudopods decreased, and irregularly shaped, dense bodies increased from the time of surgery until 12 weeks later. Administration of an acute dose of TSH at this time resulted in obvious mitotic activity and the formation of numerous pseudopods. The tissue also maintained the ability to take up radioactive iodine and to iodinate thyroglobulin. Inhibition of TSH secretion through T4 administration from the time of surgery did not affect viability. Some cellular hypertrophy persisted after 32 weeks although TSH and T4 had returned to normal. This study has shown that thyroid tissue remains viable, functional, and experimentally alterable throughout an extended period of chronic stimulation by endogenous TSH, and that it has the reserve capacity to secrete normal levels of T4 at the end of this experimental period.