Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland

A.T. Slominski, T.K. Kim, W. Li, A. Postlethwaite, Elaine Tieu, Edith Tang, Robert Tuckey

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Abstract

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) 2 D3, 20,22(OH) 2 D3, 20,23(OH) 2 D3, 20,24(OH) 2 D3, 20,25(OH) 2 D3, 20,26(OH) 2 D3, 1,20,23(OH) 3 D3 and 17,20,23(OH) 3 D3, plus 1,20(OH) 2 D3 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) 3 D3, 1,20,25(OH) 3 D3 and 1,20,26(OH) 3 D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH) 2 7DHC 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.
Original languageEnglish
Pages (from-to)14875
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

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Secosteroids
Cholesterol Side-Chain Cleavage Enzyme
Bioactivity
Cholecalciferol
Metabolism
Skin
Steroids
Hormones
Derivatives
7-dehydrocholesterol

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Slominski, A.T. ; Kim, T.K. ; Li, W. ; Postlethwaite, A. ; Tieu, Elaine ; Tang, Edith ; Tuckey, Robert. / Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. In: Scientific Reports. 2015 ; Vol. 5. pp. 14875.
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abstract = "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) 2 D3, 20,22(OH) 2 D3, 20,23(OH) 2 D3, 20,24(OH) 2 D3, 20,25(OH) 2 D3, 20,26(OH) 2 D3, 1,20,23(OH) 3 D3 and 17,20,23(OH) 3 D3, plus 1,20(OH) 2 D3 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) 3 D3, 1,20,25(OH) 3 D3 and 1,20,26(OH) 3 D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH) 2 7DHC 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.",
author = "A.T. Slominski and T.K. Kim and W. Li and A. Postlethwaite and Elaine Tieu and Edith Tang and Robert Tuckey",
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Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland. / Slominski, A.T.; Kim, T.K.; Li, W.; Postlethwaite, A.; Tieu, Elaine; Tang, Edith; Tuckey, Robert.

In: Scientific Reports, Vol. 5, 2015, p. 14875.

Research output: Contribution to journalArticle

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T1 - Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland

AU - Slominski, A.T.

AU - Kim, T.K.

AU - Li, W.

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AU - Tieu, Elaine

AU - Tang, Edith

AU - Tuckey, Robert

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M3 - Article

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SP - 14875

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

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