Expression, localization, and thyrotropin regulation of cathepsin D in human thyroid tissues.

Enzymatic activity and isoform expression of cathepsin D (cath D) were studied in 107 cytosols from various human thyroid tissues including 21 normal tissues, 12 cold benign nodules, 17 toxic adenomas, 22 samples from Graves’ disease patients, and 35 thyroid carcinomas. Cath D assay was optimized for human thyroid tissues. We found that mean cath D specific activities, expressed as units per milligrams protein minus thyroglobulin, were higher in carcinomas (P = 0.0001), toxic adenomas (P = 0.0001), and specimens from Graves’ disease patients (P = 0.0001) than in normal thyroid tissues. Mean cath D activity in carcinomas was also significantly different from that in cold benign nodules (P < 0.001) and Graves’ disease tissues (P < 0.05) but not from that of toxic adenomas. To determine possible mechanisms by which the observed increase in cath D activity might be regulated, we used Western blotting to measure relative amounts of cath D isoforms in the various thyroid tissues. We found that the 31-kDa major ...