Clinical Aspects of Steroid Conjugation

Quantification of the Endogenous Adduction Level on Hemoglobin and Correlation with Albumin Adduction via Proteomics: Multiple Exposure Markers of Catechol Estrogen

“…Catechol estrogens (CEs) are phase-one metabolites of parent estradiol (E2) and may be oxidized into quinones or semi-quinones, which are genotoxic due to their reactions with DNA to form depurinating adducts that lead to oncogenic mutations and DNA damage . These harmful metabolites are eliminated by urine or feces via phase-II metabolism that involves conjugation into hydrophilic forms, such as glucuronidation, sulfation, and methylation. , High CE levels are related to unbalanced estrogen homeostasis and are associated with a high risk of various diseases, such as breast cancer, and metabolic syndrome . In addition to their effects on the host, certain estrogen conjugates can be hydrolyzed to free forms by gut bacteria and participate in enterohepatic circulation. , Recent studies related breast cancer with the microbiota in the body, especially the gut bacteria, which play an important role in the estrogen cycle. , Regardless of the host or microbiota, it has been suggested that higher ratios of 4-hydroxylated CEs to 4-methoxylated CEs (4-OHE2/4-MeOE2) are indicators of breast cancer.…”

“…1 These harmful metabolites are eliminated by urine or feces via phase-II metabolism that involves conjugation into hydrophilic forms, such as glucuronidation, sulfation, and methylation. 2,3 High CE levels are related to unbalanced estrogen homeostasis and are associated with a high risk of various diseases, such as breast cancer, 4 and metabolic syndrome. 5 In addition to their effects on the host, certain estrogen conjugates can be hydrolyzed to free forms by gut bacteria and participate in enterohepatic circulation.…”

Simultaneous Determination of Twelve Tetrahydrocorticosteroid Glucuronides in Human Urine by Liquid Chromatography/Electrospray Ionization-Linear Ion Trap Mass Spectrometry

“…The main pathways of phase I metabolic reaction are reduction of the α,β-unsaturated carbonyl system to form tetrahydrocorticosteroids (3α-hydroxy products), oxidation and reduction at C-11, as well as reduction at C-20. These biotransformations not only increase the polarity of the molecules but also offer a site for phase II biotransformations such as glucuronidation. ,− Such phase II metabolites may make up 90% of the excreted metabolites − and are therefore an important class of conjugates for assessment of altered corticosteroid metabolism in disease conditions. The most common conjugation reaction in man is (ethereal) glucuronidation at carbon atoms C-3 or C-21.…”