EVIDENCE THAT TYPE-III IODOTHYRONINE DEIODINASE IN RAT ASTROCYTE IS ASELENOPROTEIN

A type III iodothyronine deiodinase (D-III) that inactivates thyroid h ormones has been recently cloned and identified as a selenoprotein in neonatal rat skin. However, selenium (Se) deficiency does not affect t he D-III activity in the rat placenta and decreases the D-III in the r at brain only slightly. This study examines the effect of Se on the D- III activity in cultures of rat brain astrocytes. Astrocytes were depl eted in Se by maintaining them in Se-free chemically defined medium fo r 7 days. These conditions decreased the activity of a recognized sele noprotein, glutathione peroxidase, 3-10-fold. D-III activity induced b y 12-O-tetradecanoylphorbol-13-acetate (TPA) was also decreased 2-6-fo ld. Addition of 30 nM Se to the culture medium caused a rapid increase in TPA-induced D-III activity visible within 1 h. This Se effect was maximal at 3 h (4-fold increase) and dose-dependent. Se also increased the induction of D-In by acidic Fibroblast Growth Factor, 8-bromo-cAM P, T-4, or retinoic acid. Cycloheximide blocked the effect of Se on TP A-induced D-III activity, whereas actinomycin D did not. Thus the rapi d effect of Se does not require messenger RNA synthesis but requires p rotein synthesis. We conclude that the D-III in astrocytes is probably a selenoprotein.