AGE DELAYS THYROGLOBULIN PROGRESSION TOWARDS DENSE LYSOSOMES IN THE CREAM HAMSTER THYROID

We have shown that large lysosomes appear in thyroids of aging male cr eam hamsters. To investigate the role of this lysosomal change in the age-dependent reduction in hormone secretion, thyroids of young (<4 mo nths of age) and old (>22 months of age) male and female hamsters were labeled with I-125 at near isotopic equilibrium. Changes in thyroid m orphology were analyzed by light- and electron-microscopic morphometry . Changes in thyroglobulin processing were analyzed by subcellular fra ctionation and identification of I-125-compounds by sucrose gradients and reverse-phase high-pressure liquid chromatography (HPLC). Sexual d imorphism present in thyroids of young animals became more marked upon aging. The parallel increase in thyroid weight and thyroglobulin glob ulin content was more conspicuous in old females than in old males. Tw o morphological observations were specific to old females: (1) large f ollicles with flat epithelium and evenly labeled colloid and (2) depos its 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 isopycn ic centrifugation of crude lysosomal fractions in Percoll gradients, I -125 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). I-125 in the lighter particl es was mostly found in intact thyroglobulin and in large iodopeptides. This I-125 Shift towards less dense particles was more marked in fema les than in males. These results indicate that age delays thyroglobuli n progression towards dense lysosomes and suggest that the slower traf fic of thyroglobulin in the endocytic pathway contributes to the reduc tion in thyroid hormone secretion in the aged cream hamster.