title: Effect of phthalate esters and alkylphenols on steroidogenesis in human adrenocortical H295R cells.
abstract: 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 μM 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 μM. 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(20,22)-lyase (CYP11A), 3β-hydroxysteroid dehydrogenase type II (3β-HSDII), 17α-hyroxylase/C(17,20)-lyase (CYP17), 21-hydroxylase (CYP21B) and 11β-hydroxylase (CYP11B1), were investigated. DCHP significantly inhibited CYP21B activity at 25 μM. 4-t-OP strongly inhibited CYP11A activity at 12.5 and 25 μM, and inhibited CYP17 and CYP21B at 25 μM. Similarly, 4-NP inhibited CYP11A at 25 μM and strongly inhibited CYP17 and CYP21B at 12.5 and 25 μM. Neither DCHP nor any of the alkylphenols tested altered 3β-HSDII activity.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakajin
authors.forename: S
authors.initials: S
authors.lastname: Shinoda
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Nakazawa
authors.forename: T
authors.initials: T
authors.lastname: Makino