Abstract:
: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.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Lacroix M,Hontela Adoi
10.1016/s0041-008x(03)00168-6subject
Has Abstractpub_date
2003-08-01 00:00:00pages
197-205issue
3eissn
0041-008Xissn
1096-0333pii
S0041008X03001686journal_volume
190pub_type
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