Toxicological Sciences, Vol 50, 45-53, Copyright © 1999 by Society of Toxicology
A Hood, J Liu and CD Klaassen
Reduced thyroid hormone concentrations (T4 and/or T3) and increased
thyroid-stimulating hormone (TSH) have been proposed to mediate the thyroid
tumor promoting effects of hepatic microsomal enzyme inducers (MEI) and
antithyroid drugs. TSH is known to stimulate thyroid gland function and
growth, as well as neoplasia. Thyroid weight has been used as an indicator
of thyroid gland growth in MEI studies, but little is known about the
effects of these inducers on thyroid cell proliferation. Therefore, we
determined the time-course of thyroid cell proliferation of rats treated
with MEI, and with the antithyroid drug propylthiouracil (PTU). Male
Sprague-Dawley rats were fed either a basal diet or a diet containing
phenobarbitol (PB) (1200 ppm), PCN (500 ppm), or PTU (30 ppm) for 3, 7, 14,
21, 30, 45, 60, or 90 days. PB and PCN treatments did not affect T3, but
PTU reduced T3 60%. PB and PCN treatments reduced T4 25%, whereas PTU
treatment reduced T4 90%. PB and PCN treatments increased thyroid weight
80%, and PTU increased thyroid weight 500%. TSH was not appreciably altered
in PB-treated rats, but was increased 75% and 830% in PCN- and PTU-treated
rats, respectively. Thyroid cell proliferation was increased 260, 330, and
850% in rats treated with PB, PCN, or PTU, respectively, for 7 days, but
returned to control levels by the 45th treatment day. In conclusion,
treatment with MEI that produced mild increases in TSH resulted in dramatic
increases in thyroid cell proliferation, which peaked after 7 days of
treatment and then returned to control values. This result is similar to
that of antithyroid drugs, which produce large increases in TSH. These
findings may have important implications for the role thyroid follicular
cell proliferation has in mediating the thyroid tumor promoting effects of
MEI.
ARTICLES
Effects of phenobarbital, pregnenolone-16alpha-carbonitrile, and propylthiouracil on thyroid follicular cell proliferation
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
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