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Toxicological Sciences 65, 52-61 (2002)
Copyright © 2002 by the Society of Toxicology

ENDOCRINE TOXICOLOGY

The Hypothalamo-Pituitary-Thyroid (HPT) Axis: A Target of Nonpersistent ortho-Substituted PCB Congeners

Moazzam A. Khan*, Carol A. Lichtensteiger{dagger}, Obaid Faroon{ddagger}, Moiz Mumtaz{ddagger}, David J. Schaeffer* and Larry G. Hansen*,1

* Department of Veterinary Biosciences, College of Veterinary Medicine, 2001 S. Lincoln Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; {dagger} Department of Veterinary Pathobiology, College of Veterinary Medicine, 2001 S. Lincoln Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; and {ddagger} Division of Toxicology, Agency for Toxic Substances and Disease Registry (ATSDR), 1600 Clifton Road, Atlanta, Georgia 30333

Coplanar polychlorinated biphenyls (PCBs) cause adverse effects in developing and adult animals. Less is known about the effects of nonplanar ortho-substituted PCBs. We investigated the effects of 2 nonplanar PCB congeners, 95 (2,3,6-2',5'-penta CB) or 101 (2,4,5-2',5'-penta CB), and estradiol on selected endocrine parameters. In Study 1, weanling female Sprague-Dawley (S-D) rats were given a single dose of PCB 95 ip at 4, 8, 16, and 32 mg/kg/day for 2 consecutive days and killed 24 h after the last dose. PCB 95 exposure caused a dose-dependent (p < 0.001) decrease in serum thyroxine (T4) levels. Serum thyroid stimulating hormone (TSH) concentrations did not change, but prolactin (PRL) levels increased in a nonlinear (with dose) manner. No significant changes were seen in thyroid gland morphology and pituitary lactotroph number. In Study 2, progression or regression of effects was assessed by lengthening the time and a second congener was tested. Weanling female S-D rats received a single dose of PCB 95 or PCB 101 ip at 16 and 32 mg/kg/day for 2 days and were killed 48 h after the last dose. PCB 95 and PCB 101 both decreased serum T4 (p < 0.001) and hypothalamic dopamine (DA; p < 0.05) levels. No changes were seen in serum triiodothyronine (T3), TSH, and PRL concentrations. Morphological analysis of the thyroid gland showed a decrease (p < 0.05) in colloid area in rats treated with PCB 95 or 101. However, the epithelial cell height increased only in PCB 95 treated rats. Thyroid epithelial cell proliferation increased (p < 0.05) following exposure to estradiol and PCB 95. The results suggest that the HPT axis appears to be a target of ortho-substituted PCBs. PCB 95 was more effective than PCB 101 in causing these changes.

Key Words: episodic; PCBs; thyroid; thyroxine (T4); triiodithyronine (T3); pituitary; thyroid stimulating hormone (TSH); prolactin; hypothalamus; dopamine.


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