In Vitro 2,3,7,8-Tetrachlorodibenzo-p-dioxin Interference with the Anterior Pituitary Hormone Adrenocorticortropin

Treatment of male Sprague-Dawley rats with a single oral doseof 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shownto increase serum adrenocorticotropin (ACTH) and decrease serumcorticosterone. The present in vitro study was designed to assesswhether TCDD has a direct effect on the anterior pituitary underbasal and stimulated conditions. Primary anterior pituitarycell cultures were prepared from normal 180- to 220-g male Sprague-Dawleyrats and the cultures treated with 10^–9–10^–19M TCDD. Maximal secretion of ACTH occurred between 10^–11and 10^–15 M TCDD for both medium (2-fold) and intracellular(1.5-fold) concentrations after 24 h TCDD exposure. TCDD treatmentalso caused an early (6 h) and persistent (10 days) increasein basal medium (1.4- to 2.8-fold) and intracellular (1.1- to1.7-fold) ACTH concentrations. However, while stimulation withcorticotropin-releasing hormone (CRH) increased intracellularACTH 1.5- to 1.7-fold in pituitary cells treated for 24 h with10^–9–10^–13 M TCDD, ACTH secreted into themedia was decreased by 30–50% compared with controls.Lastly, the secretagogue arginine-8-vaso-pressin (AVP), didnot increase the amount of ACTH secreted above levels observedwith basal TCDD exposure. From this study, it appears that TCDDstimulates in vitro synthesis and secretion of ACTH by the anteriorpituitary under basal conditions, but decreases the pituitary'sresponsiveness to CRH and AVP stimulation.