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Chronic treatment with polychlorinated biphenyls (PCB) during pregnancy and lactation in the rat: Part 1: Effects on somatic growth, growth hormone-axis activity and bone mass in the offspring
Authors:Daniela Cocchi  Alessandra Colciago  Francesca Pagani  Tiziana Rubino  Patrizia Bonfanti  Fabio Celotti
Institution:a Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy
b Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy
c Department of Structural and Functional Biology, University of Insubria, Varese, Italy
d INBB Research Unit, Department of Endocrinology, Pathophysiology and Applied Biology University of Milan, Italy
e Department of Environmental Sciences, University of Milan-Bicocca, Milan, Italy
Abstract:Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure.Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.
Keywords:Polychlorinated biphenyls  Growth hormone  Somatostatin  Bone  Rat
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