Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Abstract

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

Evaluation of hypothalamus‐pituitary‐thyroid axis function by chronic perchlorate exposure in male rats

“…Indeed, the increased amount of blood vessels surrounding the thyroid follicles, the colloid‐depleted follicles and the alterations in the thyrocytes shape reveal the substantial stimulus of TSH in the thyroid gland of these animals. In accordance, these morphological modifications are consistently observed in TSH‐stimulated thyroid glands, especially in the hypothyroid condition induced by iodine deficient diets . Therefore, the modifications on thyroid morphology that were observed in the perchlorate‐exposed animals could result from the inhibition of iodide transport.…”

Age delays thyroglobulin progression towards dense lysosomes in the cream hamster thyroid

“…To our surprise, Tg concentration was reduced to 11% in old female colloids, which indicates that compression of the epithelium in large follicles is not due to an excessive accumulation of Tg. Likewise, Tg content was low in macrofollicular goiters induced by diphenylthiohydantoin (Gerber et al 1994). Interestingly, we also observe that neither the increased 125 I content of older Tg, nor the age-dependent reduction in 125 I-DIT coupling into 125 I-T 4 was influenced by gender.…”

Mode of Carcinogenic Action of Pesticides Inducing Thyroid Follicular Cell Tumors in Rodents

“…Diphenylthiohydantoin inhibits 5'-monodeiodinase and enhances hepatic thyroid hormone metabolism and excretion (73). Finally, polychlorinated biphenyls enhance the hepatic metabolism and excretion of thyroid hormones while also damaging follicular cells' ability to produce thyroid hormone (45,63).…”