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 dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to increase serum adrenocorticotropin (ACTH) and decrease serum corticosterone. The present in vitro study was designed to assess whether TCDD has a direct effect on the anterior pituitary under basal and stimulated conditions. Primary anterior pituitary cell cultures were prepared from normal 180- to 220-g male Sprague-Dawley rats and the cultures treated with 10(-9)-10(-19) M TCDD. Maximal secretion of ACTH occurred between 10(-11) and 10(-15) M TCDD for both medium (2-fold) and intracellular (1.5-fold) concentrations after 24 h TCDD exposure. TCDD treatment also caused an early (6 h) and persistent (10 days) increase in basal medium (1.4- to 2.8-fold) and intracellular (1.1- to 1.7-fold) ACTH concentrations. However, while stimulation with corticotropin-releasing hormone (CRH) increased intracellular ACTH 1.5- to 1.7-fold in pituitary cells treated for 24 h with 10(-9)-10(-13) M TCDD, ACTH secreted into the media was decreased by 30-50% compared with controls. Lastly, the secretagogue arginine-8-vaso-pressin (AVP), did not increase the amount of ACTH secreted above levels observed with basal TCDD exposure. From this study, it appears that TCDD stimulates in vitro synthesis and secretion of ACTH by the anterior pituitary under basal conditions, but decreases the pituitary's responsiveness to CRH and AVP stimulation.
Bestervelt
L L
LL
Toxicology Department, NSF International, Ann Arbor, Michigan 48105, USA.
Pitt
J A
JA
Nolan
C J
CJ
Cai
Y
Y
Piper
D W
DW
Dybowski
J A
JA
Dayharsh
G A
GA
Piper
W N
WN
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000072317:Polychlorinated Dibenzodioxins; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone