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ohd, pubmed, article, human, google, scholar, serum, cas, vitamin, cypa, epidermis, adrenal, pig, metabolism, slominski, central, dhc, skin, ohdhc, samples, metabolites, vivo, fig, data, standards, detection, secosteroids, analyzed, activity, dhp, retention, size, gland, vitro, products, biochem, nature, cells, column, min, cypb, detected, waters, mol, pscc, spectra, cypaderived, tuckey, hydroxyderivatives, biological,

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nature portfolio privacy policy nature research involved author information authors myopia development advertising 0/ reprints incubation media results regional nih grants 2r01ar052190-a6 decreases nf-kappab activity appreciable 1α–hydroxylase activity tae-kang kim ultra-performance liquid chromatography social media shows anti-cancer activities show anti-melanoma activity cell-lineage dependent fashion27 lc/qtof-ms alongside cyp11a1-derived ∆7-sterols/steroids permissions hydroxy-derivatives identified illustrate lc/qtof-ms demonstrate liquid chromatography-mass spectrometry specifically 7dhp-derived species cytochrome p450-mediated metabolism cyp11a1-derived d3 hydroxymetabolites 7dhp-derived species displayed nf-kappab activity institutional animal care article slominski cytochrome p450scc-dependent metabolism 14 ng/mg protein cell-type dependent role initially pre-purified samples privacy full size image article number vitamin d2 hydroxy-derivatives anti-cancerogenic effects competing financial interests high catalytic efficiency secosteroidal pathways initiated bleomycin induced scleroderma39 trihydroxy-vitamin d3 metabolites journals search log extremely high doses anti-inflammatory effects institutional review board

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         headline:Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland
         description:To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.
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      headline:Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland
      description:To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.
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