The endocrine disrupting alkylphenols and 4,4′-DDT interfere with oestrogen conversion and clearance by mouse liver cytosol

Endocrine disrupting chemicals (EDCs) are ubiquitous compounds known for negative impacts on reproductive functions and for increasing cancer risk. EDCs are believed to cause the harmful effects in part through their inappropriate low-affinity binding to steroid receptors and other possible non-receptor mediated paradigms, however there is a need to further elucidate other mechanisms involving the direct and indirect impact of EDCs on reproductive functions. The present study examined the metabolism of 17?-oestradiol (E2) and oestrone (E1) by cell-free hepatic cytosol in the presence of alkylphenols (nonylphenol/NP and 4-tert-octylphenol/tOP), Dichlorodiphenyltrichloroethane (4,4′-DDT) and other EDCs. Tandem liquid chromatography mass spectrometry was utilised to quantitatively assess the impact of each EDC on oestrogen clearance, inter-conversions and downstream metabolism by mouse liver cytosol. The results revealed that NP and tOP (0.1-3?g/mL) significantly reduced the hepatic cytosol clearance and biotransformation of estrogens with inclination for accumulating E2, the stronger oestrogen form, than E1. Alkylphenols also caused up to a 34-fold increase in the E2/E1 ratio possibly by suppressing the hepatic E2?E1 conversion by 17?-hydroxysteroid dehydrogenase (17?HSD) types 2, 4 while displaying a weaker inhibition of E1?E2 conversion by type 1, 17?HSD. On the other hand, the pesticide 4,4′-DDT was a weaker inhibitor of clearance of oestrogens by the cytosol preparations when compared to alkylphenols, whereas chemicals such as phthalates and atrazine were ineffective. The data suggest that exposure to NP, tOP and DDT can indirectly increase the oestrogenic load by suppressing the hepatic clearance of estrogens and by elevating the E2/1 ratio and could therefore increase the risk of reproductive lesions.

Authors: El-Hefnawy T, Hernandez C, Stabile LP. ;Full Source: Reproductive Biology. 2017 May 19. pii: S1642-431X(17)30002-5. doi: 10.1016/j.repbio.2017.04.003. [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][Epub ahead of print] ;[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]