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

Abstract

We have shown that large lysosomes appear in thyroids of aging male cream hamsters. To investigate the role of this lysosomal change in the age-dependent reduction in hormone secretion, thyroids of young (<4 months of age) and old (>22 months of age) male and female hamsters were labeled with 125I at near isotopic equilibrium. Changes in thyroid morphology were analyzed by light- and electron-microscopic morphometry. Changes in thyroglobulin processing were analyzed by subcellular fractionation and identification of 125I-compounds by sucrose gradients and reverse-phase high-pressure liquid chromatography (HPLC). Sexual dimorphism present in thyroids of young animals became more marked upon aging. The parallel increase in thyroid weight and thyroglobulin content was more conspicuous in old females than in old males. Two morphological observations were specific to old females: (1) large follicles with flat epithelium and evenly labeled colloid and (2) deposits of amyloid material (possibly immunoglobulin light chain-related) between follicles. Although lysosomes were enlarged in female and male aged thyroids, they did not accumulate iodine. However, after isopycnic centrifugation of crude lysosomal fractions in Percoll gradients, 125I in old thyroids was not distributed mainly in the dense fraction L1 (lysosomes) as in young thyroids, but partly in particles of lower density (light L2 and buoyant fractions). 125I in the lighter particles was mostly found in intact thyroglobulin and in large iodopeptides. This 125I shift towards less dense particles was more marked in females than in males. These results indicate that age delays thyroglobulin progression towards dense lysosomes and suggest that the slower traffic of thyroglobulin in the endocytic pathway contributes to the reduction in thyroid hormone secretion in the aged cream hamster.

The endocytic catalysts, Rab5a and Rab7, are tandem regulators of thyroid hormone production

“…The shift of particulate iodine (reflecting iodo amino acids of Tg) from endosomes in PN tissues toward lysosomes in AAs, supports the hypothesis that Tg processing and thyroid hormone release can already occur in late endosomes of quiescent thyrocytes with moderate efficiency, as observed upon aging (22). In contrast, Tg processing by active cells is essentially achieved by lysosomes resulting in accelerated hormone production, as found in stimulated thyroid remnants (21).…”

Inhibitions of thyroidal and extra-thyroidal T3, T4 and thyroperoxidase profiles with elevations of TSH following lithium treatment in adult and aged rats

“…Moreover, lithium-induced changes were more drastic in aged than in adult rats. Age is known to delay thyroglobulin progression towards deuse of lysosome and suggests a slower traffic of thyroglobulin in the endocytic pathway resulting in the reduced thyroid hormone secretion (38). Lower levels of serum T 3 and T 4 have also been reported to decrease with age in cats (39).…”