Inhibition of cortisol secretion in dispersed head kidney cells of rainbow trout (Oncorhynchus mykiss) by endosulfan, an organochlorine pesticide

The effects of endosulfan, an organochlorine pesticide, on cortisol secretion in vitro were investigated in enzymatically dispersed head kidney cells of rainbow trout, Oncorhynchus mykiss. First, the conditions for maximal cortisol secretion were characterized by selecting the optimal concentrations of adrenocorticotropin (ACTH) (1 IU/ml) and N-6, 2'-o-dibutyryladenosine 3':5'-cyclic monophosphate (dbcAMP) (2 mM), incubation temperature (15 degrees) and time period (60 min for ACTH, 120 min for dbcAMP), number of cells per incubation well (75 x 10(6)/ml), and osmolarity of the medium (270 mosmol/L). Exposure of head kidney cells to endosulfan decreased ACTH- or dbcAMP-stimulated cortisol secretion and cell viability in a concentration-dependent pattern and the doses required to disrupt cortisol secretion were significantly lower than doses lethal to the head kidney cells. The median effective concentration of endosulfan (EC50, the dose that inhibits cortisol secretion by 50%) was 17.3 muM while the median lethal concentration (LC50, the dose that kills 50% of the cells) was 308 muM. Our study identified endosulfan as an environmental endocrine disrupting chemical that interferes with the normal secretory function of teleost interrenal steroidogenic cells. Multiple sites may be affected within the steroidogenic cells since dbcAMP could not restore cortisol secretion in endosulfan exposed cells. (C) 2001 Academic Press.