van den Hove M F, Couvreur M, Authelet M, Nève P
Cell Biology Unit CELL 7541, Université Catholique de Louvain, Christian de Duve Institute of Cellular Pathology, 75 Avenue Hippocrate, B-1200 Brussels, Belgium.
Cell Tissue Res. 1998 Oct;294(1):125-35. doi: 10.1007/s004410051162.
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.
我们已经表明，大型溶酶体出现在衰老雄性奶油仓鼠的甲状腺中。为了研究这种溶酶体变化在激素分泌随年龄下降中的作用，对年轻（<4个月龄）和年老（>22个月龄）的雄性和雌性仓鼠的甲状腺进行了近同位素平衡的125I标记。通过光镜和电镜形态计量学分析甲状腺形态的变化。通过亚细胞分级分离以及用蔗糖梯度和反相高压液相色谱（HPLC）鉴定125I化合物来分析甲状腺球蛋白加工过程的变化。年轻动物甲状腺中存在的性别二态性在衰老时变得更加明显。甲状腺重量和甲状腺球蛋白含量的平行增加在老年雌性中比在老年雄性中更明显。有两个形态学观察结果是老年雌性特有的：（1）具有扁平上皮且胶体标记均匀的大滤泡，以及（2）滤泡之间的淀粉样物质（可能与免疫球蛋白轻链相关）沉积。尽管雌性和雄性衰老甲状腺中的溶酶体都增大了，但它们不积累碘。然而，在Percoll梯度中对粗溶酶体组分进行等密度离心后，老年甲状腺中的125I不像年轻甲状腺那样主要分布在致密组分L1（溶酶体）中，而是部分分布在较低密度的颗粒（轻L2和漂浮组分）中。较轻颗粒中的125I大多存在于完整的甲状腺球蛋白和大的碘化肽中。这种125I向密度较小颗粒的转移在雌性中比在雄性中更明显。这些结果表明，年龄延缓了甲状腺球蛋白向致密溶酶体的进程，并表明甲状腺球蛋白在内吞途径中较慢的运输导致了衰老奶油仓鼠甲状腺激素分泌的减少。
