Effect of phthalate esters and alkylphenols on steroidogenesis in human adrenocortical H295R cells

We investigated the inhibitory effects of phthalate esters and alkylphenols on steroidogenesis by human adrenocortical H259R cells, a model of human steroidogenic cells. Dicyclohexyl phthalate (DCHP) at a concentration of 30 muM produced a significant decrease in the dibutyryl cAMP-stimulated cortisol secretion (76% reduction). 4-t-Pentylphenol (4-t-PP), 4-t-octylphenol (4-t-OP) and 4-nonylphenol (4-NP) also produced significant decreases in the dibutyryl cAMP-stimulated cortisol secretion by 58, 34 and 40%, respectively at 50 muM Reductions in cortisol secretion by these chemicals were dose-dependent. To elucidate the inhibitory effects of DCHP, 4-t-PP, 4-t-OP and 4-NP on cortisol secretion from H295R cells, the effects of these chemicals on various steroidogenic enzymes, such as C-20,C-22-lyase (CYP11A), 3 beta -hydroxysteroid dehydrogenase type II (3 beta -HSDII), 17 alpha -hyroxylase/ C-17,C-20-lyase (CYP17), 21-hydroxylase (CYP21B) and I I P-hydroxylase (CYP11B1), were investigated. DCHP significantly inhibited CYP21B activity at 25 muM. 4-t-OP strongly inhibited CYP11A activity at 12.5 and 25 muM, and inhibited CYP17 and CYP21B at 25 tM. Similarly, 4-NP inhibited CYP11A at 25 muM and strongly inhibited CYP17 and CYP21B at 12.5 and 25 VM. Neither DCHP nor any of the alkylphenols tested altered 3 beta -HSDII activity. (C) 2001 Elsevier Science B.V. All rights reserved.