Inhibitory effect of chlordecone and mirex on steroid synthesis in Y-1 cells.
Chlordecone is known to bring about alterations in the endocrine systems of a variety of animals. The present study was undertaken to investigate the possibility of a direct effect of the insecticide on steroid-secreting tissues. Technical grade chlordecone produced a dose-dependent inhibition of steroidogenesis in cultured mouse adrenal tumor cells (Y-1 cells) when stimulated with ACTH (IC50 = 4 X 10(-5) M), cAMP (IC50 = 2.3 X 10(-5) M), or pregnenolone (IC50 3.5 X 10(-5) M). Similar values were obtained with 99% pure chlordecone. These data suggest that chlordecone inhibited the conversion of pregnenolone into 20 alpha-dihydroprogesterone. Additional sites of action cannot be ruled out. Mirex failed to inhibit steroidogenesis which was supported by exogenous pregnenolone. At a concentration of 3 X 10(-6) M mirex inhibited cAMP induced steroidogenesis, but higher concentrations did not produce a more pronounced effect.
D000310:Adrenal Gland Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D007631:Chlordecone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D007306:Insecticides / Q000494:pharmacology*; D051379:Mice; D008917:Mirex / Q000494:pharmacology*; D011284:Pregnenolone / Q000378:metabolism / Q000494:pharmacology; D013256:Steroids / Q000096:biosynthesis*
D007306:Insecticides; D013256:Steroids; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D007631:Chlordecone; D008917:Mirex