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

Toxicol Appl Pharmacol. 1999 Oct 15;160(2):163-70. doi: 10.1006/taap.1999.8752.


The microsomal enzyme inducer (MEI), phenobarbital (PB), has been proposed to promote thyroid tumors by increasing the biotransformation and elimination of T(4), resulting in an increase in serum thyroid-stimulating hormone (TSH). In turn, TSH stimulates thyroid gland function, growth, and ultimately neoplasia. The dose-dependent effects of MEI on thyroid-follicular cell proliferation, a measure of thyroid gland growth, has not been reported. In the present study, it was hypothesized that MEIs that increase TSH would stimulate thyroid-follicular cell proliferation and the total number of thyroid-follicular cells. Male Sprague-Dawley rats were fed either a basal diet or a diet containing PB (at 300, 600, 1200, or 2400 ppm), pregnenolone-16alpha-carbonitrile (PCN) (at 200, 400, 800, or 1600 ppm), 3-methylcholanthrene (3MC) (at 50, 100, 200, or 400 ppm), or Aroclor 1254 (PCB) (at 25, 50, 100, or 200 ppm) for 7 days. PB and PCN increased TSH 65% and 95%, respectively, whereas 3MC and PCB did not appreciably affect TSH. PB and PCN increased thyroid-follicular cell proliferation 625% and 1200%, respectively, whereas 3MC and PCB did not have a consistent or appreciable effect. The total number of thyroid-follicular cells was not significantly increased by MEI treatment. In conclusion, small increases in TSH by PB and PCN produced large increases in thyroid-follicular cell proliferation, which did not result in a comparable increase in the total number of thyroid-follicular cells. Furthermore, MEI that did not increase TSH did not consistently or appreciably increase thyroid-follicular cell proliferation or cell number.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Count
  • Cell Division / drug effects
  • Chlorodiphenyl (54% Chlorine) / pharmacology
  • Enzyme Activation / drug effects
  • Hyperplasia
  • Hypertrophy
  • Male
  • Methylcholanthrene / pharmacology
  • Organ Size
  • Phenobarbital / pharmacology*
  • Pregnenolone Carbonitrile / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood


  • Triiodothyronine
  • Chlorodiphenyl (54% Chlorine)
  • Pregnenolone Carbonitrile
  • Methylcholanthrene
  • Thyrotropin
  • Thyroxine
  • Phenobarbital