Adrenocorticotrophin‐ and cyclic adenosine 3′,5′‐monophosphate‐stimulated cortisol secretion in interrenal tissue of rainbow trout exposed in vitro to DDT compounds

Abstract

Abstract-The effects of DDT compounds on the function and viability of interrenal corticosteroidogenic tissue were investigated in vitro in rainbow trout (Oncorhynchus mykiss) in a dose-response study. The o,pЈ-dichlorodiphenyldichloroethane (DDD) was the most potent of the tested chemicals in decreasing adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion by head kidney fragments compared with controls. The dbcAMP-stimulated cortisol secretion was also impaired with doses of 50 and 100 mg/L o,pЈ-DDD but not 25 mg/L. Tissue viability, estimated by the release of lactate dehydrogenase (LDH), was similar to controls at 25 mg/L and was decreased significantly at 50 and 100 mg/L o,pЈ-DDD. These results suggest that o,pЈ-DDD is an adrenotoxic compound that may disrupt the 3Ј,5Ј-monophosphate (cAMP) generation step and, at higher doses, induce irreversible cytotoxic effects. The p,pЈ-DDT induced a significant inhibition in the secretory response to ACTH and dbcAMP only at 100 mg/L, while p,pЈ-DDD had no effect on the cortisol secretion. A significantly decreased viability was detected at the higher doses of p,pЈ-DDT and p,pЈ-DDD without a detectable disruption of cortisol synthesis. The steroidogenic interrenal cells may be less sensitive to the DDT compounds tested than other cell populations within the teleost head kidney.

Regulation of acute cortisol synthesis by cAMP-dependent protein kinase and protein kinase C in a teleost species, the rainbow trout (Oncorhynchus mykiss)

“…Toxicological studies have demonstrated the disruptive effects of xenobiotics on adrenal steroidogenesis in teleosts (Ilan & Yaron 1983, Brodeur et al 1998, Hontela 1998 as well as in birds and mammals (Jönsson et al 1993, 1994, Lund 1994, Mgbonyebi et al 1994. It has also been reported that acute (60 min) non cytotoxic in vitro exposures of interrenal cells to o,p -DDD, a DDT metabolite, inhibit cortisol secretion through effects prior to cAMP formation while heavy metals such as cadmium, zinc, and mercury seem to exert their effects downstream from cAMP production in the signalling cascade leading to acute cortisol synthesis (Leblond & Hontela 1999, Benguira & Hontela 2000. These studies have shown that xenobiotics may target different intracellular steps of adrenal steroidogenesis, some of which are relevant to the intracellular signalling pathways leading to cortisol synthesis.…”

“…CytP450 hydroxylases) by cAMP, PKA or PKC has been investigated in numerous mammalian models (Schimmer 1995). However, the time course of the disruptive effects reported in recent toxicological studies in fish (Leblond & Hontela 1999, Benguira & Hontela 2000 suggests that mechanisms regulating acute cortisol synthesis may be targeted by some adrenotoxicants. Acute trophic hormone-mediated steroidogenesis calls for rapid regulation mechanisms involving intracellular messengers such as PKA and PKC and proteins that act upon the rate limiting step in cortisol synthesis in the adrenal gland: the transfer of cholesterol to the inner mitochondrial membrane (Clark et al 1994, Lin et al 1995, Stocco & Clark 1996.…”

Loss of capacity to elevate plasma cortisol in rainbow trout (Oncorhynchus mykiss) treated with a single injection of o,p′‐dichlorodiphenyldichloroethane

“…The effective doses and the mechanisms of action responsible for the decrease in plasma cortisol in fish need to be established because of the ubiquity of this organochlorine in the environment [21,22], its continued use in many countries around the world, and differences in the mechanisms of action of DDT compounds among vertebrates. There is evidence for teleosts that o,p ′‐DDD disrupts the adrenal steroidogenesis at steps upstream from the cAMP generating process within the steroidogenic enzymatic pathways since treatment with dbcAMP, a cyclic adenosine 3′,5′‐monophosphate analog, could reverse the inhibition of cortisol synthesis in the presence of o,p ′‐DDD [17,19,20]. In higher vertebrates, o,p ′‐DDD seems to target different intracellular processes.…”

“…Tilapia injected with o,p ′‐dichlorodiphenyldichloroethane ( o,p ‐DDD: 1‐[ o ‐chlorophenyl]‐1‐[ p ‐chlorophenyl]‐2,2‐dichloroethane) had lower plasma cortisol and lower response of the adrenal (interrenal) tissue to ACTH in vitro than controls [17,18]. Recently, the effects of DDT compounds on ACTH‐ and dibutyryl cyclic adenosine 3′,5′monophosphate‐stimulated cortisol secretion were characterized in vitro in adrenal tissue of rainbow trout [19,20]. Since DDT and its metabolites remain ubiquitous contaminants in the aquatic environment [21,22] and because there may be species differences in the vulnerability of the adrenal tissue to these organochlorine chemicals, we designed an experiment to determine in vivo the effects of o,p ′‐DDD on the capacity to mount the normal cortisol stress response and the physiological status of rainbow trout, a model teleost species.…”

Influence of water quality and associated contaminants on survival and growth of the endangered Cape Fear shiner (Notropis mekistocholas)

“…The DDTs are highly persistent and toxic compounds. Evidence for reproductive toxicity and adrenotoxicity in birds and mammals is prevalent, and growing evidence indicates adverse effects on the adrenal and reproductive systems in many fish [37,38]. The estimated concentrations of DDTs in water were greatest at HR1 and HR2.…”