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Bestervelt LL, Pitt JA, Piper WN: Evidence for Ah receptor mediation of increased ACTH concentrations in primary cultures of rat anterior pituitary cells exposed to TCDD. Toxicol Sci. 1998 Dec;46(2):294-9.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to increase plasma ACTH concentrations in male Sprague-Dawley rats and in male rat primary anterior pituitary cell cultures. The present study examined whether the anterior pituitary effects observed after TCDD exposure are mediated via the Ah receptor (AhR). Primary anterior pituitary cell cultures were prepared from normal 180- to 220-g male rats and the cultures treated with alpha-naphthoflavone (ANF), an antagonist; beta-naphthoflavone (BNF), an agonist; BNF + TCDD; 3,3',4,4',5-pentachlorobiphenyl (PCB), which is known to bind to the AhR; and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), which does not bind the AhR. Support for the TCDD-AhR-mediated increases in ACTH concentrations is provided by the following observations: (1) ANF inhibited both the 1.3- to 2-fold TCDD-induced increase in basal medium and intracellular ACTH concentrations and the 30% TCDD-induced decrease in medium ACTH levels and the 1.2-fold increase in intracellular ACTH levels in corticotropin-releasing hormone (CRH)-stimulated cells, (2) BNF increased basal medium (1.7-fold) and intracellular (1.3-fold) ACTH concentrations, (3) BNF + TCDD demonstrated additivity by increasing basal medium (2.4-fold) and intracellular (1.7-fold) ACTH concentrations, (4) PCB increased basal medium (1.8- to 2.1-fold) and intracellular (1.3- to 1.8-fold) ACTH concentrations and inhibited medium ACTH secretion in CRH stimulated cells by 24-43%, and (5) HCB did not effect basal or CRH stimulated medium and intracellular ACTH concentrations. From this study it appears that TCDD-induced changes in ACTH secretion and synthesis by cultured anterior pituitary cells is mediated through the Ah receptor. |
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