Effects of polycyclic musks HHCB and AHTN on steroidogenesis in H295R cells

Abstract

1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) are widely used in personal care products. Previous studies showed that HHCB and AHTN can be found in various environmental matrices and have potential endocrine disrupting effects. However, the effects on adrenocortical function of HHCB and AHTN are not fully understood. This study evaluated the influences of HHCB and AHTN on seven steroid hormones (progesterone, aldosterone, cortisol, 17α-OH-progesterone, androstenedione, 17β-estradiol, and testosterone) and 10 genes involved in steroidogenic pathways (HMGR, StAR, CYP11A1, 3βHSD2, CYP17, CYP21, CYP11B1, CYP11B2, 17βHSD, and CYP19) using the H295R cell line in the absence and presence of 8-Br-cAMP. MC2R transcription on the cell membrane was also examined to further investigate the effects of HHCB and AHTN on adrenal steroidogenesis. The results demonstrated that HHCB and AHTN could inhibit progesterone and cortisol production mainly by the suppression of 3βHSD2 and CYP21. Meanwhile, high concentrations of AHTN can affect the sensitivity of H295R cells to ACTH by disrupting MC2R transcription. Overall, the results indicate that high concentrations of HHCB and AHTN can affect steroidogenesis in vitro using the H295R cell line.