Endocrine disruptive effects of polychlorinated aromatic hydrocarbons on intestinal cholecystokinin in rats

The ubiquitous and persistent nature of polychlorinated aromatic hydrocarbo ns (PCAHs) in our environment and the risk of exposure to PCAHs have provok ed concern over their potential toxicity. In humans, exposure to PCAHs is a imed chiefly at epithelial cells residing in the intestinal mucosa, because oral intake of contaminated food is a major source of PCAHs. The purpose o f 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-p entachlorodibenzofuran (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 s how that chronic PCAH treatment significantly lowers intestinal levels of s tored CCK peptide. Intestinal CCK messenger RNA levels are not affected. In addition, 3,3',4,4',5-pentachlorobiphenyl treatment increased intestinal i nsulin-like growth factor-binding protein-3 levels in a dose-related manner . Acute 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment of intestinal CCK cel ls lowered levels of CCK-processing enzymes (i.e, prohormone convertase-1 a nd -2). Together, these data indicate that PCAHs may decrease intestinal le vels of stored CCK peptide by affecting the intestinal insulin-like growth factor system and CCK processing.