Rat thyroid hyperplasia induced by gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Endocrinology. 2003 May;144(5):2075-83. doi: 10.1210/en.2002-220737.


Effects of gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid function of offspring were investigated in the rat. Pregnant Holtzman rats, TCDD-sensitive strain, were given a single oral dose of 200 ng or 800 ng TCDD/kg on gestational day 15. Parameters related to the thyroid functions were examined on postnatal days (PNDs) 21 and 49. Serum T(4) levels in offspring decreased significantly on PND21 in the two TCDD-exposed groups but increased on PND 49 only in the high-dose group. A dose of 800 ng TCDD/kg exerted a more than 2-fold increase in serum TSH level in male offspring on PNDs 21 and 49. A significant induction of uridine diphosphate-glucuronosyltransferase-1 gene by TCDD was observed on PND 21 but returned to basal levels on PND 49. Gene expression of cytochrome P4501A1 was markedly induced in the liver treated with TCDD. Even a single oral perinatal exposure to 800 ng TCDD/kg resulted in hyperplasia of the thyroid gland of offspring on PND 49. Proliferating cell nuclear antigen immunocytochemistry also supported this finding. Thus, gestational and lactational exposure to TCDD was found to disrupt thyroid hormone homeostasis, which results in a sustained excessive secretion of TSH, followed by the hyperplasia of thyroid follicular cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Cytochrome P-450 CYP1A1 / genetics
  • Drug Administration Schedule
  • Environmental Pollutants* / administration & dosage
  • Female
  • Growth / drug effects
  • Hyperplasia
  • Lactation / physiology*
  • Liver / metabolism
  • Male
  • Monosaccharide Transport Proteins / genetics
  • Osmolar Concentration
  • Polychlorinated Dibenzodioxins* / administration & dosage
  • Pregnancy
  • Pregnancy, Animal / physiology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Strains
  • Reproduction / drug effects
  • Thyroid Diseases / chemically induced*
  • Thyroid Diseases / pathology*
  • Thyroid Gland / pathology*
  • Thyroxine / blood


  • Environmental Pollutants
  • Monosaccharide Transport Proteins
  • Polychlorinated Dibenzodioxins
  • RNA, Messenger
  • UDP-galactose translocator
  • Cytochrome P-450 CYP1A1
  • Thyroxine