INHIBITION OF HEPATIC THYROXINE 5'-MONODEIODINASE BY HUMIC ACIDS

Humic substances are implicated as a kind of environmental goitrogen, and increased prevalence of goiter has been recently noticed in the bl ackfoot disease endemic area in the southwest of Taiwan, where well wa ter is rich in humic substances. In this study we have investigated th e effects of humic substances on hepatic 5'-monodeiodinase (5'-MD) in rats to gain knowledge of such effects on thyroid hormone metabolism. Aliquots of rat liver microsome (about 5 mug of protein) were preincub ated in 0.1 M Tris buffer (pH 7.4) for 30 min with or without various concentrations (12.5-800 mug/ml) of humic acids, then incubated with t hyroxine (T4, 2.5 muM; final volume 1 ml) and dithiothreitol (DTT, 5 o r 25 mM) in the same buffer for 30 min. The 3,5,3'-triiodothyronine (T 3) generated during incubation was quantified by radioimmunoassay (RIA ) of ethanol extracts of the incubation mixture. Humic acids caused a dose-dependent inhibition of hepatic T4 5'-monodeiodination. The mean dose (+/- SD) that caused a 50% inhibition of 5'-MD activity was 58 +/ - 6 mug/ml (n = 8). The inhibition was not a result of the depletion o f T4 during incubation of T4 with humic acids. Free radical scavengers - catalase (300 U/ml) and superoxide dismutase (100 U/ml)- had no eff ect on the inhibition of hepatic T4 5'-monodeiodination induced by hum ic acids. Our data suggest that humic acids influence thyroid hormone metabolism by inhibiting hepatic 5'-MD activity.