title: Effects of in vitro exposures to cadmium, mercury, zinc, and 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane on steroidogenesis by dispersed interrenal cells of rainbow trout (Oncorhynchus mykiss).
abstract: Numerous environmental xenobiotics can act as endocrine disrupters in wildlife species. Fish chronically exposed to pollutants exhibit a deficiency in the synthesis of cortisol, a glucocorticosteroid hormone secreted by interrenal steroidogenic cells in response to ACTH by a mechanism mediated by cAMP. The capacity of a series of heavy metals (CdCl2, ZnCl2, HgCl2, and CH3HgCl) and 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane (o,p'-DDD) to disrupt cortisol secretion was determined in dispersed interrenal cells of rainbow trout (Oncorhynchus mykiss) exposed in vitro to the toxicant, by measuring cortisol secretion stimulated with ACTH or dibutiryl-cAMP (dbcAMP) and by assessing cell viability. The effect of cadmium in presence of zinc on the interrenal cells was also determined. The median lethal concentration (LC50, dose that kills 50% of the cells), median effective concentration (EC50, dose that inhibits cortisol secretion by 50%), and LC50/EC50 ratio were determined for each chemical to compare its endocrine toxicity and to test the specificity of the toxicants to act as endocrine disrupters. HgCl2 had the lowest EC50 and LC50; it was the most toxic of the chemicals tested. The LC50/EC50 ratio was the highest for ZnCl2 and CdCl2, indicating that these toxicants had the most specific endocrine toxicity. The mechanism of toxicity of heavy metals on cortisol-secreting cells involves a site situated downstream from the step generating cAMP, while o,p'-DDD seemed to impair a step located between adenyl cyclase activation and the ACTH binding. No evidence for a protector effect of zinc against cadmium toxicity was found.
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D006854:Hydrocortisone / Q000096:biosynthesis*; D008628:Mercury / Q000633:toxicity*; D008939:Mitotane / Q000633:toxicity*; D017686:Oncorhynchus mykiss; D015032:Zinc / Q000633:toxicity*