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Thyroid gland function was investigated in rats with experimental hyperuricemia. Data obtained indicate that dyshormonal changes are secondary ones and their development depends on the state of purine metabolism. Administration of allopyrinol, an uric acid depressant drug, improved thyroid gland function.
The thyroid gland controls the progress of metamorphosis, although other hormones influence metamorphic rate, including melatonin, which may coordinate metamorphosis with seasonal and light conditions. Melatonin directly antagonized the action of thyroxine (T4) in promoting regression of tadpole tail tips in vitro, and this study sought to determine if it affects the thyroid axis of tadpoles as well. In an experiment sampling at 8-hr intervals for 24 hr, after melatonin treatment (15 micrograms/day for 12 days) of premetamorphic Rana pipiens tadpoles at approximately 1100 hr on 18L:6D, thyroid follicle cell height and lumen diameter were lowered by melatonin, but follicle cell proliferation was not significantly depressed. In a second experiment conducted under the same conditions, but sampling at 3-hr intervals for 24 hr, melatonin significantly lowered follicle cell labeling index and suppressed its ultradian (7.6 hr) rhythm, while shifting the peak of follicle lumen diameter to the dark instead of the light. Thus, melatonin tended to depress the thyroid of young tadpoles and suppress or shift its rhythms. Melatonin (10 micrograms/day for 5 days) injected into prometamorphic Rana catesbeiana tadpoles at 1930 hr on 18L:6D significantly altered subsequent in vitro thyroid function as determined by radioimmunoassay of media collected at intervals for 54 hr from cultured thyroids of injected control and melatonin groups, and a noninjected control group. Melatonin decreased T4 secretion during the first 30 hr, but not during the last 24 hr of culture, suppressed 3,5,3'-triidothyronine (T3) secretion for 12 hr, and then raised T3 output into the media above the control for the remainder of the culture period, increasing the T3:T4 ratio. Injection alone increased both T3 and T4 secretion for the first 30 hr, but did not change the T3:T4 ratio. The findings show that exogenous melatonin administered in vivo significantly modulated thyroid activity and morphometry directly and/or indirectly and comprise the first demonstration of an effect of melatonin on the amphibian thyroid gland.
Differentiated carcinoma of the thyroid gland is regarded as an indolent disease. However, this notion is dispelled when the population is stratified according to age, gross and microscopic tumoral characteristics and according to the occurrence of local and distant metastases in the early postoperative period. The adverse effect of local and distant recurrences on survival time has been emphasized in multiple series from the United States and Europe. However, the critical question that has yet to be answered is whether or not inadequately treated differentiated carcinomas of the thyroid gland seemingly cured in younger patients will recur as aggressive, malignant tumors when the same patients reach the graying golden years. A provisional answer to this question may indeed be found in the incidence of early postoperative nodal and distant recurrence rates. Some authors have concluded that the extent of operative treatment does not have a major influence on the course of differentiated carcinoma of the thyroid gland. This conclusion prompted the present follow-up study of 250 patients with differentiated carcinoma of the thyroid gland to examine the clinical course and results of therapy. We report a cumulative mortality rate of 2.4 per cent and a recurrence rate of 1.6 per cent, consisting of a 1.2 per cent incidence of cervical nodal recurrence and a distant recurrence rate of 0.4 per cent (one patient), after a median follow-up period of seven years and a mean of six years. Since there were no differences in treatment and outcome in 191 patients we studied who had papillary and 59 who had follicular carcinoma, they were analyzed as a single group for this report. Total thyroidectomy was the minimal treatment of all operable patients. In addition, 21.0 per cent required a modified dissection of the neck and 8.4 per cent of the patients had postoperative radioactive iodine administered to ablate either remnants of normal tissue or previously undetected metastases to cervical nodes or lungs. Potential factors contributing to improved local and distant recurrence rates included early detection of disease, especially in children who had irradiation and who were recalled and screened (34 per cent in this series); the use of needle aspiration cytologic study, leading to earlier diagnosis and treatment; total thyroidectomy, and the effective use of radioactive iodine administered as a single large dose within the first six months after thyroidectomy.
In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats.
Slices of porcine thyroid gland were incubated with arachidonic acid and ionophore A 23187. This led to the formation of 5-hydroxy-eicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE and leukotriene B4 (LTB4). Time course studies demonstrated that levels of detected LTB4 reached a plateau after 30 min and that in parallel with the synthesis of this compound, greater amounts of 5-HETE was formed. The present results demonstrate the formation of lipoxygenase products in the porcine thyroid gland, indicating possible physiological/pathophysiological roles for these compounds in this organ.
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Bcl-2 family proteins are important regulators of apoptosis. To clarify a role of apoptosis and the expression of Bcl-2 family proteins in the pathogenesis of subacute thyroiditis (SAT), we evaluated the expression of Bcl-2, Bax, and Bak by immunohistochemistry and apoptosis by in situ end labeling of fragmented DNA in thyroid tissues from 11 patients with SAT. Apoptotic nuclei were found in granulomas, especially in macrophages/histiocytes and lymphocytes, and in the regenerating follicular cells, but were rarely found in the area of fibrosis. The mean (+/-SD) percentage of apoptotic follicular cells was significantly greater in SAT than that in controls (1.4 +/- 0.8% vs. 0.4 +/- 0.6%). Bcl-2, Bak, and Bax were strongly expressed in the granulomas and regenerating thyroid follicular cells from patients with SAT. Bcl-2 and Bak, but not Bax, were expressed in follicular cells from normal controls. The percentage of apoptotic cells and the expression of Bax in follicular cells did not correlate with age or serum levels of thyroid hormones, C-reactive protein, or thyroglobulin. These data suggest that apoptosis may be involved in the development of SAT and that Bax expression in regenerating thyrocytes may be important for the recovery of SAT.
We have investigated whether nuclear T3 receptors exist in the thyroid cell. Nuclear proteins extracted from porcine thyroid nuclei with 0.4 mol/l KCl were incubated with [125I]T3. The mixture was then analysed by sucrose density gradient ultracentrifugation which revealed that the T3-binding proteins migrated at the same position of 3.6 S as rat liver nuclear T3 receptors. Fractionation by high performance liquid chromatography using a size exclusion column and an ion exchanger column also demonstrated elution patterns of T3-binding similar to those of the rat liver receptor. Scatchard plots of crude nuclear extracts from porcine thyroid represented a curvilinear pattern. However, when the nuclear proteins partially purified by a DEAE column chromatography were analysed, a single binding component was found; the association constant was 4.1 x 10(10) l/mol and the maximal binding capacity was 602 fmolT3/mg protein. Displacement study with several T3 analogues showed a highly selective affinity for L-T3. Cultured rat thyroid cells of the FRTL-5 line also contained a single class of saturable, high affinity T3-binding site. Subconfluent cells in 100-mm dishes were incubated with increasing amounts of [125I]T3 at 37 degrees C for 3 h and radioactive T3 in isolated nuclei was counted. Scatchard analysis of data showed that the association constant and the maximal binding capacity were 3.44 +/- 0.63 x 10(10) l/mol and 63.7 +/- 17.8 fmolT3/mg protein, respectively. These results strongly suggest that there are nuclear T3 receptors, indistinguishable from the hepatic T3 receptors, in the porcine thyroid and rat FRTL-5 cells.
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