Differential effects of microsomal enzyme inducers on in vitro thyroxine (T-4) and triiodothyronine (T-3) glucuronidation

Microsomal enzyme inducers that increase UDP-glucuronosyl-transferase (UDP- GT) activity are suspected to affect the thyroid gland by increasing the gl ucuronidation of T-4, which reduces serum thyroxine (T-4). In response to r educed serum T-4, serum thyroid-stimulating hormone (TSH) increases. Howeve r, not all microsomal enzyme inducers that reduce serum T-4 produce an incr ease in serum TSH. We have shown that serum TSH is increased the most in ra ts treated with the microsomal enzyme inducers phenobarbital (PB) or pregne nolone-16 alpha-carbonitrile (PCN), whereas TSH is affected less in rats tr eated with 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB). It is unclear why serum TSH is differentially affected by various microsomal enzyme indu cers. We propose that the glucuronidation of T-3 might be the reason serum TSH is increased by some microsomal enzyme inducers but not by others. Male Sprague-Dawley rats were fed either a basal diet or a diet containing PB ( at 300, 600, 1200, or 2400 ppm), PCN (at 200, 400, 800, or 1600 ppm), 3MC ( at 50, 100, 200, or 400 ppm), or PCB (at 25, 50, 100, or 200 ppm) for 7 day s; and T-4 and T-3 UDP-GT activities were then determined. T-4 UDP-GT activ ity was increased in rats treated with PB (1208), PCN (250 to 400%), 3MC (4 00 to 600%), or PCB (300 to 430%). In contrast, T-3 UDP-GT activity was inc reased in rats treated with PB (90%) or PCN (120 to 200%), whereas 3MC and PCB treatments did not have an appreciable effect. In conclusion, different ial effects on T-3 glucuronosyltransferase activity were found in rats trea ted with microsomal enzyme inducers.