Effect of environmental chemicals on steroidogenesis in human adrenal carcinoma cell

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We investigated the effects of phthalate esters, alkylphenols, phytochemichals and organotin compounds on steroidogenesis by human adrenocortical H259R cells, a model of human steroidogenic cells. DOT and its metabolite, dicyclohexyl phthalate (DCHP), 4-t-pentylphenol (4-t-PP), 4-t-octylphenol (4-t-OP) and 4-nonylphenol (4-NP) produced a significant decrease in the dibutyryl cAMP-stimulated cortisol secretion. Flavonoids, such as 6-hydroxyflavone, 4'-hydroxyflavone, apigenin, daidzein, genistein and formononetin also significantly decreased cortisol production of H295R cells. Furthermore, bis (tributyltin) oxide (TBTO), tributyltin chloride (TBT) and dibutyltin dichlonde (DBT) produced a significant decrease in the dibutyryl cAMP-stimulated cortisol production. To elucidate the inhibitory mechanism of these chemicals on cortisol production from H295R cells, the effects of these chemicals on various steroidogenic enzymes, such as C_<20, 22>-lyase (P450scc), 3β-hydroxysteroid dehydrogenase type II (3β-HSD II), 17α-hyroxylase/C_<17, 20>-lyase (P450c17), 21-hydroxylase (P450c21) and 11β-hydroxylase (P45011β), were investigated.