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Moazzam A Khan

Publications and source records attributed to Moazzam A Khan.

2 recordsLinked to original sources

Ortho-substituted polychlorinated biphenyl (PCB) congeners (95 or 101) decrease pituitary response to thyrotropin releasing hormone.

Polychlorinated biphenyl compounds (PCBs) are global environmental contaminants that cause disruption of the endocrine system in humans and wildlife. Recently, we reported that acute exposures to ortho-PCB congeners 95 (2,3,6-2',5') or 101 (2,4,5,-2',5') causes changes in the performance of the hypothalamo-pituitary-thyroid (HPT)-axis in developing rats through mechanism(s) not yet clear. The functionality of the HPT-axis was evaluated by using the thyrotropin releasing hormone (TRH) test following acute exposure to PCBs 95 or 101. Weanling female rats received PCBs 95 or 101 intraperitoneally (ip) at 32 mg/kg for 2 consecutive days and synthetic TRH was given 48 h after the last dose. Serum thyroxine (T4) levels decreased following exposure to both the congeners. In PCB 95-treated rats, serum thyroid stimulating hormone (TSH) levels were elevated in response to TRH, but were only 40% of the control response to TRH. No significant changes were seen in serum prolactin (PRL), hypothalamic dopamine (DA), thyroid gland morphology, or epithelial cell proliferation. It is suggested that these congeners, interfere with the HPT-axis by causing a subnormal response of the pituitary and thyroid to TRH stimulation.

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The hypothalamo-pituitary-thyroid (HPT) axis: a target of nonpersistent ortho-substituted PCB congeners.

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.

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