Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain.
Polychlorinated biphenyls (PCBs) are a class of industrial compounds consisting of paired phenyl rings with various degrees of chlorination. They are now ubiquitous, persistent environmental contaminants that are routinely found in samples of human and animal tissues and are known to affect brain development. The effects of PCBs on brain development may be attributable, at least in part, to their ability to reduce circulating levels of thyroid hormone. However, the developmental effects of PCB exposure are not fully consistent with hypothyroidism. Because some individual PCB congeners interact strongly with various thyroid hormone binding proteins, several investigators have speculated that these congeners may be producing thyroid hormone-like effects on brain development. Therefore, we tested whether a mixture of PCBs, Aroclor 1254 (A1254), would produce an antithyroid or thyromimetic effect on the expression of known thyroid hormone-responsive genes in the developing brain. Pregnant female rats were fed various doses of A1254 (0, 1, 4, and 8 mg/kg) from gestational day 6 to weaning on postnatal day (P) 21. Pups derived from these dams were sampled on P5, P15, and P30. Total T4 was reduced by A1254 in a dose-dependent manner, but body weight of the pups or dams was not affected. The expression of RC3/Neurogranin and myelin basic protein was not affected by A1254 on P5 or P30. However, on P15, RC3/Neurogranin was elevated by A1254 in a dose-dependent manner, and myelin basic protein expression followed this general pattern. These data clearly demonstrate that the developmental effects of PCB exposure are not simply a function of PCB-induced hypothyroidism.
Zoeller
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Biology Department, University of Massachusetts, Morrill Science Center, Amherst 01003, USA. tzoeller@bio.umass.edu
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D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D004676:Myelin Basic Protein / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D051579:Neurogranin; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013963:Thyroid Hormones / Q000494:pharmacology*
D002148:Calmodulin-Binding Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; C496651:Nrgn protein, rat; D015347:RNA Probes; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D051579:Neurogranin; D011078:Polychlorinated Biphenyls