Thyroid hormone metabolism in cultured monkey hepatocarcinoma cells. Monodeiodination activity in relation to cell growth.

Thyroid hormone metabolism was studied in mono- layers of monkey hepatocarcinoma cells (NCLP-GE) in which the major metabolite of thyroxine (T4) is 3,3’,5’- triiodo-L-thyronine (e3), and those of 3,5,3’-triiodo-~-thyronine (T3) are 3,3’-diiodo-~-thyronine (3,3’-T~) and 3’-monoiodo-~-thyronine (3’-T1). Cells were induced to synchronize by culturing in medium deficient in isoleucine (De(-)) or in isoleucine and glutamine (ne(-)Gln(-)), In these growth-arrested (mainly G I phase) cells, the metabolic pathway through nonphenolic ring deiodination of lzBI-labeled precursors (namely, the conversion of T4 to r T 3 , r T 3 to 3’,5‘-T~, T3 to 3,3’-T2, and 3,3’-T2 to 3’-T1) was markedly increased. A slight increase in 5“deiodination (rT3 to 3,3‘-T~) was also observed. Lineweaver-Burk analysis using cell ho- mogenate containing dithiothreitol revealed that the apparent K,,, for 5-deiodination (T4 to rT3, 0.059 PM, and T3 to 3,3’-T4, 0.034 PM) and for 5’-deiodination (rT3 to 3,3’-Tz, 1.3 CM)