POSTTRANSLATIONAL INHIBITION OF ITO CELL TYPE-I COLLAGEN PRODUCTION BY TRIIODOTHYRONINE

Increased Ito cell collagen production occurs during in vivo liver fib rogenesis. Regulation of the overproduction of collagen was studied in cultured rat hepatic Ito cells, which resemble the myofibroblast asso ciated with liver fibrosis. Previous studies suggest that the steroid hormones, retinoic acid, and glucocorticoids may have antifibrogenic p roperties in vitro and in vivo when used at pharmacological doses. The ir potential roles at physiological levels are not well understood. Th e current study examined the potential regulation of the overproductio n of type I collagen in cultured rat hepatic Ito cells by another ster oid hormone, 3,5,3'-triiodo-L-thyronine (T3). T3 induced a 3.4-fold re duction in type I collagen production. The effect was dose dependent a nd was maximal with physiological levels of T3 (10(-9) M). The effect of T3 was independent of any suppression in total protein synthesis. T he mechanism of the suppressive effect of T3 on collagen production wa s explored and was found to be at a posttranslational level. This stud y suggests that the inhibitory effects of T3 on type I collagen produc tion are likely caused by enhanced intracellular turnover of type I co llagen.