Endocrine disruptive effects of polychlorinated aromatic hydrocarbons on intestinal cholecystokinin in rats.
The ubiquitous and persistent nature of polychlorinated aromatic hydrocarbons (PCAHs) in our environment and the risk of exposure to PCAHs have provoked concern over their potential toxicity. In humans, exposure to PCAHs is aimed chiefly at epithelial cells residing in the intestinal mucosa, because oral intake of contaminated food is a major source of PCAHs. The purpose of this study, therefore, was to examine the effects of chronic exposure to various PCAHs [i.e. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and 2,2'4,4'5,5'-hexachlorobiphenyl (PCB-153)], given alone or as mixtures, on intestinal cholecystokinin (CCK) peptide and messenger RNA levels. We show that chronic PCAH treatment significantly lowers intestinal levels of stored CCK peptide. Intestinal CCK messenger RNA levels are not affected. In addition, 3,3',4,4',5-pentachlorobiphenyl treatment increased intestinal insulin-like growth factor-binding protein-3 levels in a dose-related manner. Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment of intestinal CCK cells lowered levels of CCK-processing enzymes (i.e. prohormone convertase-1 and -2). Together, these data indicate that PCAHs may decrease intestinal levels of stored CCK peptide by affecting the intestinal insulin-like growth factor system and CCK processing.
Department of Surgery, University of Texas Medical Branch, Galveston 77555-0725, USA.
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D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology; D002460:Cell Line; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006841:Hydrocarbons, Aromatic / Q000494:pharmacology*; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects*; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013381:Subtilisins / Q000378:metabolism
D001572:Benzofurans; D053379:Chromogranin A; D002864:Chromogranins; D006841:Hydrocarbons, Aromatic; D006843:Hydrocarbons, Chlorinated; D018972:Insulin-Like Growth Factor Binding Protein 3; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D002766:Cholecystokinin; D011078:Polychlorinated Biphenyls; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; C023035:3,4,5,3',4'-pentachlorobiphenyl; C038890:2,3,4,7,8-pentachlorodibenzofuran; C014024:2,4,5,2',4',5'-hexachlorobiphenyl