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Steroid-Metabolizing Cytochrome P450 (CYP) Enzymes in the Maintenance of Cholesterol and Sex Hormone Levels
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- Pettersson, Hanna, 1968- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Steroid P450 group
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- Norlin, Maria, Docent (thesis advisor)
- Uppsala universitet,Avdelningen för farmaceutisk biokemi
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- Wikvall, Kjell, Professor (thesis advisor)
- Uppsala universitet,Avdelningen för farmaceutisk biokemi
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- ISBN 9789155475185
- Uppsala : Acta Universitatis Upsaliensis, 2009
- English 51 s.
- Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 96
- Doctoral thesis (other academic/artistic)
Abstract
Subject headings
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- The enzymes CYP27A1 and CYP7B1 are widely expressed in various human tissues and perform catalytic reactions in cholesterol homeostasis and endocrine signaling. We have investigated the metabolism of a synthetic oxysterol. In this study, we show that CYP27A1 is the enzyme responsible for a 28-hydroxylation of this oxysterol and that the rate of CYP27A1-mediated metabolism is relatively slow. This may give an explanation for the prolonged inhibitory effects on cholesterol biosynthesis that have been shown for this oxysterol. The current study contributes to the knowledge of synthetically produced oxysterols and their potential use as cholesterol lowering drugs. In two studies we investigated CYP7B1-mediated metabolism of different sex hormones. Our data indicate that CYP7B1 may carry out a previously unknown catalytic reaction involving an androgen. Taken together the data suggest that varying steroid concentrations in cells and tissues may be important for CYP7B1-dependent metabolism of sex hormones and sex hormone precursors. CYP7B1-mediated hydroxylation of sex hormones may influence the cellular levels of these steroids and may be a potential pathway for elimination of the steroids from the cell. Some known CYP7B1 substrates are agonists for ERα and ERβ but the reported role(s) of CYP7B1 for ER action are not fully understood. In the last study we investigated the role(s) of CYP7B1-mediated metabolism for ER-mediated action. Our data indicate that CYP7B1-mediated conversion of steroids that affect ER-mediated response into their 7α-hydroxymetabolites will result in loss of action. This indicates that CYP7B1 may have an important role for regulation of ER-mediated processes in the body. In summary, results from this thesis contribute to the knowledge on the metabolism of synthetic oxysterols of potential use as cholesterol lowering drugs and the role(s) of CYP7B1-mediated metabolism for processes related to the functions of sex hormones.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- CYP27A1
- CYP7B1
- cytochrome P450
- estrogen receptor
- androgen receptor
- cholesterol
- sex hormone
- hydroxylation
- steroid metabolism
- regulation of steroid levels
- Pharmaceutical biochemistry
- Farmaceutisk biokemi
- Farmaceutisk biokemi
- Pharmaceutical Biochemistry
Publication and Content Type
- vet (subject category)
- dok (subject category)
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