Effects of microsomal enzyme inducers on thyroid-follicular cell proliferation, hyperplasia, and hypertrophy

The microsomal enzyme inducer (MEI), phenobarbital (PB), has been proposed to promote thyroid tumors by increasing the biotransformation and eliminati on of T-4, resulting in an increase in serum thyroid-stimulating hormone (T SH). In turn, TSH stimulates thyroid gland function, growth, and ultimately neoplasia. The dose-dependent effects of MEI on thyroid-follicular cell pr oliferation, a measure of thyroid gland growth, has not been reported. In t he present study, it was hypothesized that MEIs that increase TSH would sti mulate thyroid-follicular cell proliferation and the total number of thyroi d-follicular cells. Male Sprague-Dawley rats were fed either a basal diet o r a diet containing PB (at 300, 600, 1200, or 2400 ppm), pregnenolone-16 al pha-carbonitrile (PCN) (at 200, 400, 800, or 1600 ppm), 3-methylcholanthren e (3MC) (at 50, 100, 200, or 400 ppm), or Aroclor 1254 (PCB) (at 25, 50, 10 0, or 200 ppm) for 7 days. PB and PCN increased TSH 65% and 95%, respective ly, whereas 3MC and PCB did not appreciably affect TSH. PB and PCN increase d thyroid-follicular cell proliferation 625% and 1200%, respectively, where as 3MC and PCB did not have a consistent or appreciable effect. The total n umber of thyroid-follicular cells was not significantly increased by MEI tr eatment. In conclusion, small increases in TSH by PB and PCN produced large increases in thyroid-follicular cell proliferation, which did not result i n a comparable increase in the total number of thyroid-follicular cells. Fu rthermore, MEI that did not increase TSH did not consistently or appreciabl y increase thyroid-follicular cell proliferation or cell number. (C) 1999 A cademic Press.