Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes
Open accessAbstract
The discovery that 7-dehydrocholesterol (7DHC) is an excellent substrate for cytochrome P450scc (CYP11A1) opens up new possibilities in biochemistry. To elucidate its biological significance we tested ex vivo P450scc-dependent metabolism of 7DHC by tissues expressing high and low levels of P450scc activity, placenta and epidermal keratinocytes, respectively. Incubation of human placenta fragments with 7DHC led to its conversion to 7-dehydropregnenolone (7DHP), which was inhibited by dl-aminoglutethimide, and stimulated by forskolin. Final proof for P450scc involvement was provided in isolated placental mitochondria where production of 7DHP was almost completely inhibited by 22R-hydroxycholesterol. 7DHC was metabolized by placental mitochondria at a faster rate than exogenous cholesterol, under both limiting and saturating conditions of substrate transport, consistent with higher catalytic efficiency (k(cat)/K(m)) with 7DHC as substrate than with cholesterol. Ex vivo experiments showed five 5,7-dienal intermediates with MS spectra of dihydroxy and mono-hydroxy-7DHC and retention time corresponding to 20,22(OH)(2)7DHC and 22(OH)7DHC. The chemical structure of 20,22(OH)(2)7DHC was defined by NMR. 7DHP was further metabolized by either placental fragments or placental microsomes to 7-dehydroprogesterone as defined by UV, MS and NMR, and to an additional product with a 5,7-dienal structure and MS corresponding to hydroxy-7DHP. Furthermore, epidermal keratinocytes transformed either exogenous or endogenous 7DHC to 7DHP. 7DHP inhibited keratinocytes proliferation, while the product of its pholytic transformation, pregcalciferol, lost this capability. In conclusion, tissues expressing P450scc can metabolize 7DHC to biologically active 7DHP with 22(OH)7DHC and 20,22(OH)(2)7DHC serving as intermediates, and with further metabolism to 7-dehydroprogesterone and (OH)7DHP.
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CYP11A1 catalyzes cleavage of the 7DHC side chain to produce 7DHP.
“CYP11A1 catalyzes the cleavage of the side chain of 7DHC to produce 7-dehydropregnenolone (7DHP)”
From The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions (2014) · cites this paper as [40]
7DHP inhibits HaCaT keratinocyte proliferation in a dose-dependent manner, while pregnacalciferol shows little or no antiproliferative activity.
“7DHP inhibited the proliferation of HaCaT keratinocytes in a dose-dependent manner, with pregnacalciferol (pD) showing little or no antiproliferative activity”
From The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions (2014) · cites this paper as [40]
Adrenal glands, placenta, and epidermal keratinocytes can carry out CYP11A1-dependent conversions of these substrates.
“Adrenal glands, placenta, and epidermal keratinocytes can also carry out these conversions and 7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
7DHC, ergosterol, lumisterol 3, and vitamins D3 and D2 serve as substrates for CYP11A1.
“Studies, initially with purified enzyme, reveal that 7-dehydrocholesterol (7DHC), ergosterol, lumisterol 3, and vitamins D3 and D2 also serve as substrates for CYP11A1, with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum.
“7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
7DHC is a better substrate for CYP11A1 than cholesterol, while vitamins D3 and D2 are poorer substrates.
“with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
The rate of 7DHC transfer to the inner mitochondrial membrane site of CYP11A1 action by StAR protein is slightly higher than that for cholesterol.
“The rate of 7DHC transfer to the inner mitochondrial membrane site of CYP11A1 action by the StAR protein is also slightly higher than that for cholesterol [8].”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
CYP11A1 metabolizes 7DHC via the pathway 7DHC → 22-hydroxy-7DHC → 20,22-dihydroxy-7DHC → 7-dehydropregnenolone.
“Subsequent studies performed with purified bovine and human recombinant CYP11A1 and isolated mitochondria from the adrenal glands and placentae have demonstrated the following pathway for the metabolism of 7DHC: 7DHC→22-hydroxy-7DHC[22(OH)7DHC]→20,22-dihydroxy-7DHC[20,22(OH)27DHC→7DHP] [8,14,22,23].”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Molecular modeling using the crystal structure of human CYP11A1 bound to 20R,22R-dihydroxycholesterol showed that 7DHC docked with the C22 hydrogen closer to the heme iron than the C20 hydrogen, consistent with initial hydroxylation at C22 being favored.
“7DHC was docked to the crystal structure of CYP11A1 in place of the 20R,22R-dihydroxycholesterol. It showed that the C22 hydrogen was closer to the heme iron than the hydrogen at C20, consistent with initial hydroxylation at C22 being favored.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1.
“Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Human CYP11A1 has a slightly higher catalytic efficiency with 7DHC as substrate than with cholesterol.
“In fact, human CYP11A1 has a slightly higher catalytic efficiency with 7DHC as a substrate (higher Kcat/Km) than with cholesterol, indicating that 7DHC can be used preferentially by the enzyme depending on its availability [8,14].”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Cultured human (HaCaT) epidermal keratinocytes and primary pig epidermal keratinocytes metabolize 7DHC to 7DHP without addition of exogenous 7DHC.
“Final in vitro evidence that 7DHC is metabolized to 7DHP in the skin was obtained using cultured human (HaCaT) epidermal keratinocytes, and primary pig epidermal keratinocytes where products were detected without the addition of exogenous 7DHC [8].”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Human CYP11A1 produces two other hydroxy-7DHC metabolites whose identity remains to be established, and neither corresponds to 20(OH)7DHC.
“It should be noted that we also detected production of two other hydroxy-7DHC metabolites by human CYP11A1 of which the identity remains to be established [8]. Neither of them corresponded to 20 (OH)7DHC as demonstrated by their different retention times.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
CYP11A1-dependent 7DHC metabolism is possible in the human placenta in vivo.
“The most recent and extensive studies performed on human placentae and bovine adrenal glands, clearly confirmed the above studies and provided additional evidence that CYP11A1-dependent 7DHC metabolism is possible in the human placenta in vivo [8].”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
Ex utero incubations of human placentae and ex vivo incubations of pig adrenal glands with 7DHP result in its transformation to 7-dehydroprogesterone.
“Ex-utero incubations of human placentae [8] and ex-vivo incubations of pig adrenal glands [23] with 7DHP resulted in its transformation to 7-dehydroprogesterone.”
From Novel activities of CYP11A1 and their potential physiological significance (2015) · cites this paper as [8]
CYP11A1 action on 7DHC also produces 22-hydroxy-7DHC and 20,22-dihydroxy-7DHC.
“additional products of its action on 7DHC are 22-hydroxy-7DHC and 20,22-dihydroxy-7DHC [189, 190]”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [190]
7DHP can be metabolized by steroidogenic enzymes to several steroidal 5,7-dienes or derivatives.
“7DHP can be metabolized by steroidogenic enzymes to several steroidal 5,7-dienes or their derivatives [188–191].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [190]
These 5,7-dienes can be produced in tissues expressing CYP11A1, with some detectable in human epidermis, serum and pig adrenal glands.
“These 5,7-dienes (including their precursors) can be produced in tissues expressing CYP11A1 [189, 190] with some of them being detectable in the human epidermis, serum and pig adrenal glands [152].”
From The serum vitamin D metabolome: what we know and what is still to discover (2019) · cites this paper as [190]
CYP11A1 converts 7-dehydrocholesterol by hydroxylation at C22 and then C20, side-chain cleavage, and further metabolism of 7-dehydropregnenolone by existing steroidogenic enzymes.
“7DHC (7-dehydrocholesterol) can be metabolized by CYP11A1 through hydroxylation at C22 followed by C20, cleavage of the site chain and subsequent metabolism of the 7DHP (7dehydropregnenolone) by existing steroidogenic enzymes [54, 162, 163] (Fig. 5).”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [163]
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Slominski, A. T., Slominski, R. M., Raman, C., Chen, J. Y., Athar, M., & Elmets, C. A. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00147.2022 · Cited by 195 · see citing works
Self-citationOn the role of skin in the regulation of local and systemic steroidogenic activities
Slominski, A. T., Manna, P. R., & Tuckey, R. C. (2015) · Steroids · doi:10.1016/j.steroids.2015.04.006 · Cited by 183 · see citing works
Self-citationSlominski, A. T., Kim, T.-K., Li, W., Yi, A.-K., Postlethwaite, A., & Tuckey, R. C. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.10.012 · Cited by 170 · see citing works
Self-citationVitamin D, vitamin D receptor and tissue barriers
Zhang, Y., Wu, S., & Sun, J. (2013) · Tissue Barriers · doi:10.4161/tisb.23118 · Cited by 164 · see citing works
Vitamin D receptor(s): In the nucleus but also at membranes?
Zmijewski, M. A., & Carlberg, C. (2020) · Experimental Dermatology · doi:10.1111/exd.14147 · Cited by 164 · see citing works
Kim, T., Kleszczyński, K., Janjetović, Z., Sweatman, T. W., Lin, Z., Li, W., Reiter, R. J., Fischer, T. W., & Slominski, A. T. (2013) · The FASEB Journal · doi:10.1096/fj.12-224691 · Cited by 162 · see citing works
Self-citationExtra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders
Slominski, R. M., Tuckey, R. C., Manna, P. R., Jetten, A. M., Postlethwaite, A., Raman, C., & Slominski, A. T. (2020) · Genes & Immunity · doi:10.1038/s41435-020-0096-6 · Cited by 155 · see citing works
Self-citationPhotoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives
Slominski, A. T., Chaiprasongsuk, A., Janjetović, Z., Kim, T., Stefan, J., Slominski, R. M., Hanumanthu, V. S., Raman, C., Qayyum, S., Song, Y., et al. (2020) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-020-00913-6 · Cited by 150 · see citing works
Self-citationGuengerich, F. P. (2015) · Springer eBooks · doi:10.1007/978-3-319-12108-6_9 · Cited by 150 · see citing works
Local Melatoninergic System as the Protector of Skin Integrity
Slominski, A. T., Kleszczyński, K., Semak, I. V., Janjetović, Z., Zmijewski, M. A., Kim, T., Slominski, R. M., Reiter, R. J., & Fischer, T. W. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151017705 · Cited by 145 · see citing works
Self-citationNeuroendocrine Aspects of Skin Aging
Bocheva, G., Slominski, R. M., & Slominski, A. T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112798 · Cited by 137 · see citing works
Self-citationSlominski, A. T., Brożyna, A. A., Zmijewski, M. A., Jóźwicki, W., Jetten, A. M., Mason, R. S., Tuckey, R. C., & Elmets, C. A. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.3 · Cited by 136 · see citing works
Self-citationNeuro–immuno–endocrinology of the skin: how environment regulates body homeostasis
Slominski, R. M., Raman, C., Jetten, A. M., & Slominski, A. T. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01107-x · Cited by 133 · see citing works
Self-citationSteroid biosynthesis in adipose tissue
Li, J., Papadopoulos, V., & Vihma, V. (2015) · Steroids · doi:10.1016/j.steroids.2015.03.016 · Cited by 130 · see citing works
The Impact of Vitamin D on Skin Aging
Bocheva, G., Slominski, R. M., & Slominski, A. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22169097 · Cited by 129 · see citing works
Self-citationEpidermal lipids: key mediators of atopic dermatitis pathogenesis
Bhattacharya, N., Sato, W. J., Kelly, A., Ganguli-Indra, G., & Indra, A. K. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.04.001 · Cited by 128 · see citing works
Slominski, A. T., Kim, T., Janjetović, Z., Brożyna, A. A., Zmijewski, M. A., Xu, H., Sutter, T. R., Tuckey, R. C., Jetten, A. M., & Crossman, D. K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103072 · Cited by 119 · see citing works
Self-citationBiological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin
Slominski, A. T., Kim, T., Janjetović, Z., Slominski, R. M., Li, W., Jetten, A. M., Indra, A. K., Mason, R. S., & Tuckey, R. C. (2024) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2024.04.022 · Cited by 109 · see citing works
Self-citationSlominski, A. T., Kim, T.-K., Shehabi, H. Z., Tang, E. K. Y., Benson, H. A. E., Semak, I., Lin, Z., Yates, C. R., Wang, J., Li, W., et al. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.12.012 · Cited by 100 · see citing works
Self-citationOn the role of classical and novel forms of vitamin D in melanoma progression and management
Slominski, A. T., Brożyna, A. A., Skobowiat, C., Zmijewski, M. A., Kim, T., Janjetović, Z., Oak, A. S. W., Jóźwicki, W., Jetten, A. M., Mason, R. S., et al. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.06.013 · Cited by 99 · see citing works
Self-citationThe significance of CYP11A1 expression in skin physiology and pathology
Slominski, R. M., Raman, C., Elmets, C. A., Jetten, A. M., Slominski, A. T., & Tuckey, R. C. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111238 · Cited by 97 · see citing works
Self-citationCytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Slominski, A. T., Zmijewski, M. A., Semak, I. V., Zbytek, B., Pisarchik, A. V., Li, W., Zjawiony, J. K., & Tuckey, R. C. (2014) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/18715206113139990308 · Cited by 91 · see citing works
Self-citationVitamin D Signaling in Psoriasis: Pathogenesis and Therapy
Brożyna, A. A., Slominski, R. M., Nedoszytko, B., Zmijewski, M. A., & Slominski, A. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158575 · Cited by 84 · see citing works
Self-citationSlominski, A. T., Kim, T.-K., Hobrath, J. V., Janjetovic, Z., Oak, A. S. W., Postlethwaite, A., Lin, Z., Li, W., Takeda, Y., Jetten, A. M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10202-7 · Cited by 82 · see citing works
Self-citationCutaneous glucocorticosteroidogenesis: securing local homeostasis and the skin integrity
Slominski, A. T., Manna, P. R., & Tuckey, R. C. (2014) · Experimental Dermatology · doi:10.1111/exd.12376 · Cited by 79 · see citing works
Self-citationSlominski, A. T., Janjetovic, Z., Kim, T.-K., Wasilewski, P., Rosas, S., Hanna, S., Sayre, R. M., Dowdy, J. C., Li, W., & Tuckey, R. C. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.01.014 · Cited by 77 · see citing works
Self-citationNovel vitamin D photoproducts and their precursors in the skin
Slominski, A., Kim, T.-K., Zmijewski, M. A., Janjetovic, Z., Li, W., Chen, J., Kusniatsova, E. I., Semak, I., Postlethwaite, A., Miller, D. D., et al. (2013) · Dermato-Endocrinology · doi:10.4161/derm.23938 · Cited by 76 · see citing works
Self-citationMalignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling
Slominski, R. M., Kim, T., Janjetović, Z., Brożyna, A. A., Podgórska, E., Dixon, K. M., Mason, R. S., Tuckey, R. C., Sharma, R., Crossman, D. K., et al. (2024) · Cancers · doi:10.3390/cancers16122262 · Cited by 74 · see citing works
Self-citationEvolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage
Kim, T., Slominski, R. M., Pyza, E., Kleszczyński, K., Tuckey, R. C., Reiter, R. J., Holick, M. F., & Slominski, A. T. (2024) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.13091 · Cited by 68 · see citing works
Self-citationCYP11A1 in skin: an alternative route to photoprotection by vitamin D compounds
Tongkao-on, W., Carter, S., Reeve, V. E., Dixon, K. M., Gordon-Thomson, C., Halliday, G. M., Tuckey, R. C., & Mason, R. S. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2014.11.015 · Cited by 63 · see citing works
Self-citationSlominski, A. T., Kim, T., Slominski, R. M., Song, Y., Janjetović, Z., Podgórska, E., Reddy, S. B., Song, Y., Raman, C., Tang, E. K. Y., et al. (2022) · The FASEB Journal · doi:10.1096/fj.202200578r · Cited by 61 · see citing works
Self-citationMultiple functions of syncytiotrophoblast mitochondria
Martı́nez, F., Olvera-Sánchez, S., Esparza-Perusquía, M., Gómez-Chang, E., & Flores-Herrera, Ó. (2015) · Steroids · doi:10.1016/j.steroids.2015.09.006 · Cited by 61 · see citing works
Relevance of Vitamin D in Melanoma Development, Progression and Therapy
Brożyna, A. A., Hoffman, R. M., & Slominski, A. T. (2019) · Anticancer Research · doi:10.21873/anticanres.13976 · Cited by 61 · see citing works
Self-citationCurrent LC–MS methods and procedures applied to the identification of new steroid metabolites
Marcos, J., & Pozo, Ó. J. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.12.012 · Cited by 58 · see citing works
Chen, J., Wang, J., Kim, T., Tieu, E. W., Tang, E. K. Y., Lin, Z., Kovacic, D., Miller, D. D., Postlethwaite, A. E., Tuckey, R. C., et al. (2014) · PubMed · Cited by 55 · see citing works
Self-citationSlominski, A. T., Brożyna, A. A., Zmijewski, M. A., Janjetović, Z., Kim, T., Slominski, R. M., Tuckey, R. C., Mason, R. S., Jetten, A. M., Guroji, P., et al. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-46227-7_13 · Cited by 54 · see citing works
Self-citationDifferential antitumor effects of vitamin D analogues on colorectal carcinoma in culture
Wierzbicka, J., Binek, A., Ahrends, T., KA, J. D. N., SZYDŁOWSKA, A., Turczyk, L., Wasiewicz, T., Wierzbicki, P., Sądej, R., Tuckey, R. C., et al. (2015) · International Journal of Oncology · doi:10.3892/ijo.2015.3088 · Cited by 51 · see citing works
Self-citationVitamin D derivatives enhance cytotoxic effects of H2O2 or cisplatin on human keratinocytes
Piotrowska, A., Wierzbicka, J., Ślebioda, T., Woźniak, M., Tuckey, R. C., Slominski, A. T., & Żmijewski, M. A. (2016) · Steroids · doi:10.1016/j.steroids.2016.04.002 · Cited by 48 · see citing works
Self-citationFan, J., & Papadopoulos, V. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076701 · Cited by 48 · see citing works
Wierzbicka, J., Piotrowska, A., & Zmijewski, M. A. (2014) · Acta Biochimica Polonica · doi:10.18388/abp.2014_1830 · Cited by 48 · see citing works
Pang, S., Wu, H., Wang, Q., Cai, M., Shi, W., & Shang, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098283 · Cited by 46 · see citing works
Neuro-immune-endocrine functions of the skin: an overview
Nejati, R., Kovacic, D., & Slominski, A. T. (2013) · Expert Review of Dermatology · doi:10.1586/17469872.2013.856690 · Cited by 45 · see citing works
Self-citationTieu, E. W., Tang, E. K. Y., Chen, J., Li, W., Nguyen, M. N., Janjetovic, Z., Slominski, A., & Tuckey, R. C. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.09.032 · Cited by 44 · see citing works
Self-citationLumisterol is metabolized by CYP11A1: discovery of a new pathway
Tuckey, R. C., Slominski, A. T., Cheng, C. Y. S., Chen, J., Kim, T.-K., Xiao, M., & Li, W. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.08.004 · Cited by 43 · see citing works
Self-citationThe long winding road to the safer glucocorticoid receptor (GR) targeting therapies
Lesovaya, E. A., Chudakova, D. A., Baida, G. E., Михайловна, Ж. Е., Игоревич, К. К., Геннадиевна, Я. М., & Budunova, I. V. (2022) · Oncotarget · doi:10.18632/oncotarget.28191 · Cited by 43 · see citing works
Jenkinson, C., Desai, R., Slominski, A. T., Tuckey, R. C., Hewison, M., & Handelsman, D. J. (2021) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2021-0441 · Cited by 39 · see citing works
Self-citationP450 Enzymes in Steroid Processing
Auchus, R. J., & Miller, W. L. (2015) · Springer eBooks · doi:10.1007/978-3-319-12108-6_12 · Cited by 39 · see citing works
Hänel, A., Neme, A., Malinen, M., Hämäläinen, E., Malmberg, H.-R., Etheve, S., Tuomainen, T., Virtanen, J. K., Bendik, I., & Carlberg, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-78288-0 · Cited by 37 · see citing works
Wasiewicz, T., Piotrowska, A., Wierzbicka, J., Slominski, A. T., & Zmijewski, M. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092583 · Cited by 32 · see citing works
Self-citationNeurosteroidogenic enzymes: CYP11A1 in the central nervous system
Lin, Y. C., & Papadopoulos, V. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100925 · Cited by 32 · see citing works
Wang, S., Liu, W., Pang, X., Dai, S., & Liu, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072028 · Cited by 31 · see citing works
Zabul, P., Woźniak, M., Slominski, A. T., Preis, K., Górska‐Ponikowska, M., Korożan, M., Wieruszewski, J., Zmijewski, M. A., Zabul, E., Tuckey, R. C., et al. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160613043 · Cited by 29 · see citing works
Self-citationShin, M. H., Lee, Y., Kim, M. K., Lee, D. H., & Chung, J. H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105449 · Cited by 29 · see citing works
Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19
Qayyum, S., Slominski, R. M., Raman, C., & Slominski, A. T. (2022) · Nutrients · doi:10.3390/nu14224779 · Cited by 27 · see citing works
Self-citationBeneficial health effects of ultraviolet radiation: expert review and conference report
Riedmann, U., Dibben, C. J. L., de Gruijl, F. R., Gorman, S., Hart, P. H., Hoel, D. G., Levy, C., Lindqvist, P. G., Norval, M., Parikh, S., et al. (2025) · Photochemical & Photobiological Sciences · doi:10.1007/s43630-025-00743-6 · Cited by 22 · see citing works
Self-citationHolick, M. F., & Slominski, A. T. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91386-7.00006-4 · Cited by 22 · see citing works
Self-citationAlternative pathways for vitamin D metabolism
Slominski, A. T., Tuckey, R. C., Jenkinson, C., Li, W., & Jetten, A. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91386-7.00001-5 · Cited by 21 · see citing works
Self-citationMitochondrial potassium channels: A novel calcitriol target
Olszewska, A., Sieradzan, A. K., Bednarczyk, P., Szewczyk, A. M., & Zmijewski, M. A. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00299-0 · Cited by 21 · see citing works
Editorial: Steroids and Secosteroids in the Modulation of Inflammation and Immunity
Slominski, A. T., Mahata, B., Raman, C., & Bereshchenko, O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.825577 · Cited by 21 · see citing works
Self-citationXue, Y., Ying, L., Horst, R. L., Watson, G. L., & Goltzman, D. (2015) · Journal of Investigative Dermatology · doi:10.1038/jid.2015.297 · Cited by 20 · see citing works
On the role of environmental humidity on cortisol production by epidermal keratinocytes
Zhu, G. G., Janjetović, Z., & Slominski, A. T. (2013) · Experimental Dermatology · doi:10.1111/exd.12275 · Cited by 17 · see citing works
Self-citationJee, D., Kim, E. C., Cho, E., & Arroyo, J. G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157501 · Cited by 16 · see citing works
Vitamin D: A Potential Star for Treating Chronic Pancreatitis
Zheng, M., & Gao, R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.902639 · Cited by 16 · see citing works
Is Vitamin D Signaling Regulated by and Does It Regulate Circadian Rhythms?
Slominski, A. T., Slominski, R. M., Kamal, M., Holick, M. F., Tuckey, R. C., Reiter, R. J., Li, W., & Jetten, A. M. (2025) · The FASEB Journal · doi:10.1096/fj.202503003r · Cited by 15 · see citing works
Self-citationTuckey, R. C., Tang, E. K. Y., Chen, Y. A., & Slominski, A. T. (2021) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.105929 · Cited by 15 · see citing works
Self-citationTao, S., Zhang, Y., Wang, Q., Qiao, C., Deng, W., Liang, S., Wei, J., Wei, W., Yu, H., Li, X., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.969575 · Cited by 11 · see citing works
Urinary cysteinyl progestogens: Occurrence and origin
Marcos, J., Pol, M., Fabregat, A., Ventura, R., Renau, N., Hanzu, F. A., Casals, G., Marfà, S., Martín, B. B., Barceló, A., et al. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.04.015 · Cited by 11 · see citing works
Noyola-Martínez, N., Halhali, A., Zaga‐Clavellina, V., Olmos‐Ortiz, A., Larrea, F., & Barrera, D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.11.015 · Cited by 11 · see citing works
Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria
Olszewska, A. M., & Zmijewski, M. A. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101891 · Cited by 10 · see citing works
Chen, J., Slominski, A. T., Miller, D. D., & Li, W. (2013) · Dermato-Endocrinology · doi:10.4161/derm.24339 · Cited by 8 · see citing works
Self-citationBorecka, O., Rhodes, L. E., Webb, A. R., Dutton, J. J., & Fraser, W. D. (2022) · Photochemical & Photobiological Sciences · doi:10.1007/s43630-022-00274-4 · Cited by 5 · see citing works
Smith–Lemli–Opitz syndrome: From cholesterol deficiency to sterol-dependent signaling dysregulation
Akhmetzyanova, E. R., Rizvanov, A. A., & Mukhamedshina, Y. O. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107082 · Cited by 1 · see citing works
Peer, G. D. G., Leal, E. D. S., Raj, V. S., Chang, C.-M., & Pandey, R. P. (2023) · Food Chemistry Advances · doi:10.1016/j.focha.2023.100323 · Cited by 1 · see citing works
- Authors
- Slominski, A. T., Kim, T.-K., Chen, J., Nguyen, M. N., Li, W., Yates, C. R., Sweatman, T., Janjetovic, Z., & Tuckey, R. C.
- Affiliations
- University of Tennessee Health Science Center (US)
- The University of Western Australia (AU)
- Corresponding author
- Slominski, Andrzej T.
- ORCID
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 44
- Issue
- 11
- Pages
- 2003-2018
- ISSN
- 1357-2725 (ISSN-L)
- PMC
- PMC3520099
- OpenAlex
- W2010930504
- Cited by
- 81
- References
- 55
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 1
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- NIH (R01AR052190, 1R01AR056666-01A2)
- University of Western Australia
- College of Pharmacy at the University of Tennessee Health Science Center
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Keywords
- 7-dehydrocholesterol, cytochrome P450scc, CYP11A1, pregnanediol, placenta, epidermal keratinocytes, cholesterol metabolism
- MeSH terms
- Epidermal Cells, Adolescent, Adult, Animals, Cholesterol Side-Chain Cleavage Enzyme, Chromatography, High Pressure Liquid, Dehydrocholesterols, Female, Colforsin, Humans, Microsomes, Mitochondria, Magnetic Resonance Spectroscopy, Placenta, Pregnancy, Pregnenolone, Mass Spectrometry, Time Factors, Keratinocytes, Sus scrofa, Metabolic Networks and Pathways, Young Adult
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