The organochlorine o,p'-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchus mykiss).
The mechanisms of action of o,p'-DDD on adrenal steroidogenesis were investigated in vitro in rainbow trout (Oncorhynchus mykiss). Acute exposures to o,p'-DDD inhibited ACTH-stimulated cortisol secretion while cell viability decreased significantly only at the highest concentration tested (200 microM o,p'-DDD). Stimulation of cortisol secretion with a cAMP analogue (dibutyryl-cAMP) was inhibited at a higher concentration than that needed to inhibit ACTH-stimulated cortisol synthesis in cells exposed to o,p'-DDD. Forskolin-stimulated cortisol secretion and cAMP production, and NaF-stimulated cAMP production were inhibited in a concentration-dependent manner by o,p'-DDD. In contrast, basal cortisol secretion was stimulated while basal cAMP production was unaffected by o,p'-DDD. Pregnenolone-stimulated cortisol secretion was enhanced by o,p'-DDD at a physiologically relevant pregnenolone concentration, while o,p'-DDD inhibited cortisol secretion when a pharmacological concentration of pregnenolone was used. Our results suggest that the cAMP generation step is a target in o,p'-DDD-mediated disruption of ACTH-stimulated adrenal steroidogenesis in rainbow trout but that other downstream targets such as steroidogenic enzymes responsible for cortisol synthesis might also be affected.
Lacroix
Martin
M
Département des Sciences Biologiques, Université du Québec à Montréal, TOXEN Research Center, C.P. 8888, succ. Centre-Ville, Montréal, Quebec, Canada.
Hontela
Alice
A
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006727:Hormone Antagonists / Q000633:toxicity*; D006854:Hydrocortisone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008939:Mitotane / Q000633:toxicity*; D017686:Oncorhynchus mykiss; D011284:Pregnenolone / Q000494:pharmacology; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D005576:Colforsin; D011284:Pregnenolone; D008939:Mitotane; D012969:Sodium Fluoride; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D006854:Hydrocortisone