TCDD ALTERS PITUITARY-ADRENAL-FUNCTION .2. EVIDENCE FOR DECREASED BIOACTIVITY OF ACTH

The present study assessed the ability of primary cultures of rat ante rior pituitary cells to secrete bioactive ACTH in the presence of 2, 3 , 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). The bioactivity of the secr eted pituitary cell ACTH was determined by its ability to stimulate se cretion of corticosterone from primary cultures of rat adrenal cells. ACTH from basal or CRH stimulated pituitary cells treated with TCDD wa s found to be less capable of stimulating corticosterone secretion fro m primary rat adrenal cell cultures than equimolar concentrations of A CTH purchased from a commercial supplier. Corticosterone secretion fro m adrenal cell cultures treated with ACTH from basal or CRH stimulated pituitary cell cultures exposed to TCDD was decreased by 60 and 70%, respectively. The decreased ability to stimulate corticosterone secret ion can be overcome when extracts of ACTH from pituitary cell cultures treated with TCDD are supplemented with commercial ACTH. These findin gs indicate that TCDD may alter the bioactivity of secreted ACTH from the anterior pituitary gland.