Age-related Changes in Thyroid Structure and Function in Sprague-Dawley Rats

Abstract

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.

Chronic Estradiol Exposure Modulates Thyroid Structure and Decreases T₄ and T₃ Serum Levels in Middle-Aged Female Rats

“…We suppose that this noticeable difference in response to chronic EDP treatment between the central and peripheral follicles increased with advancing age, mostly due to exclusion of the peripheral follicles from active function in thyroid hormone synthesis and secretion. This assumption is consistent with a previous description of age-related changes in morphology of aged rat thyroid glands [24], as well as with the finding that old mouse thyroid contained a great number of ‘cold’, enlarged, distended follicles, that had lost their normal capacity to iodinate thyroglobulin and to respond to TSH [25, 26]. …”

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity

“…Thyroid tissue of SO rats was characterized by the presence of inactive follicles, distended with dense colloid. Rao-Rupanagudi et al (1992) and other researchers (Cizza et al 1992, Mariotti et al 1995 also reported similar histological changes and progressive loss of follicular tissue with advancing age in the thyroid of male Sprague-Dawley or Fisher rats respectively with significant decreases in free serum TH levels. At the ultrastructural level, both in SO and in Orx middleaged rats, besides numerous follicular cells with typical organization of cell organelles, quite a few thyrocytes were characterized by dilated and distended RER cisternae.…”

Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratins and VEGF. The role of nigella in refinement

“…The decrease in the T3 and T4 levels is the direct outcome of the decrease in the follicular cell number. The degenerative changes of the thyroid gland of aged Sprague-Dawley rats with concomitant decrease in the glandular function were reported earlier [6]. On the contrary, serum level of TSH exhibited a significant increase in the late adult control and senile rats.…”

“…Connective tissue could replace destroyed structures and degenerated follicles that more often occur in aging [6].…”

“…In thyroids of old rats and humans, many follicles do not contain colloid or fuse to form large irregular structures [3,5]. Moreover, there is an obvious increment in the content of interstitial fibrous connective tissue enriched with many blood vessels in aged thyroids [6]. Increased size and number of follicles were also found in the humped camel [7].…”