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Rat Thyroid Hyperplasia Induced by Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

Environmental Health Sciences Division (N.N., Y.M., M.S., C.T.), National Institute for Environmental Studies, Tsukuba 305-8506, Japan; Endocrine Disruptors and Dioxin Research Project (J.Y., Y.M., C.T.), National Institute for Environmental Studies, Tsukuba 305-8506, Japan; Core Research for Evolutional Science and Technology (J.Y., Y.M., C.T.), Japan Science and Technology, Kawaguchi 332-0012, Japan; and Institute of Clinical Medicine (M.S.), University of Tsukuba, Tsukuba 305-0006, Japan

Address all correspondence and requests for reprints to: Noriko Nishimura, Ph.D., Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. E-mail: nishimura.noriko{at}nies.go.jp.

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 T₄ 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.

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