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  1. Book ; Online ; E-Book: Steroid Biochemistry

    Penning, Trevor M.

    2023  

    Author's details Trevor M. Penning
    Keywords Biochemistry ; Steroids
    Subject code 547.7
    Language English
    Size 1 online resource (482 pages)
    Edition First edition.
    Publisher Academic Press
    Publishing place Cambridge, MA
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    ISBN 9780443185977 ; 0443185972
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Steroid 5β-reductase (AKR1D1): Purification and characterization.

    Penning, Trevor M

    Methods in enzymology

    2023  Volume 689, Page(s) 277–301

    Abstract: In mammals there are two 3-oxo-4-ene steroid reductases that generate either A/B-trans or A/B cis-ring junctions in the steroid nucleus known as steroid 5α- and 5β- reductases, respectively. There is only one steroid 5β- reductase in each species and ... ...

    Abstract In mammals there are two 3-oxo-4-ene steroid reductases that generate either A/B-trans or A/B cis-ring junctions in the steroid nucleus known as steroid 5α- and 5β- reductases, respectively. There is only one steroid 5β- reductase in each species and these are members of the aldo-keto-reductase (AKR) protein superfamily. The corresponding human enzyme is AKR1D1, and it plays an essential role in bile-acid biosynthesis. Germline mutations in AKR1D1 give rise to bile-acid deficiency. Because of its central role in steroid metabolism and need for detailed structure-function studies there is a need to purify the enzyme to homogeneity and in high yield. We report the purification of milligram amounts of crystallographic quality homogeneous recombinant protein for structure-function studies and its characterization.
    MeSH term(s) Animals ; Humans ; Oxidoreductases/chemistry ; Steroids/chemistry ; Steroids/metabolism ; Bile Acids and Salts ; Mammals/metabolism
    Chemical Substances Oxidoreductases (EC 1.-) ; Steroids ; Bile Acids and Salts
    Language English
    Publishing date 2023-04-27
    Publishing country United States
    Document type Journal Article
    ISSN 1557-7988
    ISSN (online) 1557-7988
    DOI 10.1016/bs.mie.2023.04.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Chemical carcinogenesis

    Penning, Trevor M.

    (Current cancer research)

    2011  

    Author's details Trevor M. Penning ed
    Series title Current cancer research
    Language English
    Size XV, 440 S. : Ill., graph. Darst.
    Publisher Humana Press
    Publishing place New York u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT016781281
    ISBN 978-1-61737-994-9 ; 1-61737-994-8 ; 9781617379956 ; 1617379956
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2011 A 1487 order for loan Magazin

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  4. Article ; Online: Letter to the Editor From Penning and Detlefsen "Hydroxyeicosatetraenoic Acid Controls Androgen Reduction in Diverse Types of Human Epithelial Cells".

    Penning, Trevor M / Detlefsen, Andrea J

    Endocrinology

    2023  Volume 164, Issue 5

    MeSH term(s) Humans ; Androgens/pharmacology ; Testosterone ; Dihydrotestosterone ; Epithelial Cells
    Chemical Substances Androgens ; 5-hydroxy-6,8,11,14-eicosatetraenoic acid (467RNW8T91) ; Testosterone (3XMK78S47O) ; Dihydrotestosterone (08J2K08A3Y)
    Language English
    Publishing date 2023-03-28
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqad052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Role of Human Aldo-Keto Reductases and Nuclear Factor Erythroid 2-Related Factor 2 in the Metabolic Activation of 1-Nitropyrene via Nitroreduction in Human Lung Cells.

    Su, Anthony L / Penning, Trevor M

    Chemical research in toxicology

    2023  Volume 36, Issue 2, Page(s) 270–280

    Abstract: 1-Nitropyrene (1-NP) is a constituent of diesel exhaust and classified as a group 2A probable human carcinogen. The metabolic activation of 1-NP by nitroreduction generates electrophiles that can covalently bind DNA to form mutations to contribute to ... ...

    Abstract 1-Nitropyrene (1-NP) is a constituent of diesel exhaust and classified as a group 2A probable human carcinogen. The metabolic activation of 1-NP by nitroreduction generates electrophiles that can covalently bind DNA to form mutations to contribute to cancer causation. NADPH-dependent P450 oxidoreductase (POR), xanthine oxidase (XO), aldehyde oxidase (AOX), and NAD(P)H/quinone oxidoreductase 1 (NQO1) may catalyze 1-NP nitroreduction. We recently found that human recombinant aldo-keto reductases (AKRs) 1C1-1C3 catalyze 1-NP nitroreduction.
    MeSH term(s) Humans ; Activation, Metabolic ; Aldo-Keto Reductases/metabolism ; Lung/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Vehicle Emissions
    Chemical Substances 1-nitropyrene (TD1665I8Q4) ; Aldo-Keto Reductases (EC 1.1.1.-) ; NF-E2-Related Factor 2 ; Vehicle Emissions ; NFE2L2 protein, human
    Language English
    Publishing date 2023-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/acs.chemrestox.2c00337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Insulin-Induced AKR1C3 Induces Fatty Acid Synthase in a Model of Human PCOS Adipocytes.

    Paulukinas, Ryan D / Penning, Trevor M

    Endocrinology

    2023  Volume 164, Issue 5

    Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. In PCOS, insulin resistance and hyperandrogenism could drive the increased risk for cardiometabolic disease. Aldo-keto reductase family 1 member C3 (AKR1C3) is induced by ... ...

    Abstract Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. In PCOS, insulin resistance and hyperandrogenism could drive the increased risk for cardiometabolic disease. Aldo-keto reductase family 1 member C3 (AKR1C3) is induced by insulin in PCOS adipocytes and is the predominant enzyme for potent androgen formation causing ligand-dependent androgen receptor (AR) activation. AR induces fatty acid synthase (FASN), a central enzyme for de novo lipogenesis. To investigate how insulin signaling induces AKR1C3 to promote lipid overload through induction of FASN, we used differentiated human Simpson-Golabi-Behmel syndrome adipocytes as a model for PCOS adipocytes. Induction of AKR1C3 and FASN was shown to be dependent on phosphoinositide 3-kinase/protein kinase B/ mammalian target of rapamycin/nuclear factor-erythroid 2-related factor 2 using pharmacological and genetic manipulation. FASN induction was shown to be AKR1C3 and AR dependent. Monofunctional AKR1C3 inhibitors, which competitively inhibit AKR1C3, did not block FASN induction, whereas bifunctional inhibitors, which competitively inhibit AKR1C3 and attenuate AR signaling by increasing AR degradation and ubiquitination, did suggesting a nonenzymatic role for AKR1C3 to stabilize AR. AKR1C3 and AR interacted as seen by co-immunoprecipitation, proximity ligation assay, and co-occupancy on FASN locus using chromatin immunoprecipitation-quantitative polymerase chain reaction assays in a ligand-dependent and ligand-independent manner. In the absence of androgens, bifunctional inhibitors prevented lipid droplet formation, whereas monofunctional inhibitors did not. We propose that AKR1C3 has 2 roles in PCOS: to catalyze potent androgen formation in adipocytes promoting hyperandrogenism and to induce FASN by stabilizing AR in the absence of androgens. AKR1C3 may be a therapeutic target for bifunctional inhibitors to reduce cardiometabolic disease in PCOS women.
    MeSH term(s) Humans ; Female ; Aldo-Keto Reductase Family 1 Member C3/metabolism ; Androgens/pharmacology ; Androgens/metabolism ; Polycystic Ovary Syndrome ; Insulin ; Hyperandrogenism ; Ligands ; Phosphatidylinositol 3-Kinases ; Adipocytes/metabolism ; Cardiovascular Diseases
    Chemical Substances Aldo-Keto Reductase Family 1 Member C3 (EC 1.1.1.357) ; Androgens ; Insulin ; Ligands ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; AKR1C3 protein, human (EC 1.1.1.357)
    Language English
    Publishing date 2023-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqad033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Germline Mutations in Steroid Metabolizing Enzymes: A Focus on Steroid Transforming Aldo-Keto Reductases.

    Detlefsen, Andrea J / Paulukinas, Ryan D / Penning, Trevor M

    International journal of molecular sciences

    2023  Volume 24, Issue 3

    Abstract: Steroid hormones synchronize a variety of functions throughout all stages of life. Importantly, steroid hormone-transforming enzymes are ultimately responsible for the regulation of these potent signaling molecules. Germline mutations that cause ... ...

    Abstract Steroid hormones synchronize a variety of functions throughout all stages of life. Importantly, steroid hormone-transforming enzymes are ultimately responsible for the regulation of these potent signaling molecules. Germline mutations that cause dysfunction in these enzymes cause a variety of endocrine disorders. Mutations in
    MeSH term(s) Male ; Humans ; Aldo-Keto Reductases/genetics ; Germ-Line Mutation ; Oxidoreductases/metabolism ; Steroids/metabolism ; Hormones ; Membrane Proteins/genetics ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics
    Chemical Substances Aldo-Keto Reductases (EC 1.1.1.-) ; Oxidoreductases (EC 1.-) ; Steroids ; Hormones ; SRD5A2 protein, human (EC 1.3.99.5) ; Membrane Proteins ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (EC 1.3.99.5)
    Language English
    Publishing date 2023-01-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24031873
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Genotoxicity of

    Penning, Trevor M

    Toxicology research

    2017  Volume 6, Issue 6, Page(s) 740–754

    Abstract: ... ...

    Abstract o
    Language English
    Publishing date 2017-09-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2684701-2
    ISSN 2045-4538 ; 2045-452X
    ISSN (online) 2045-4538
    ISSN 2045-452X
    DOI 10.1039/C7TX00223H
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Dehydroepiandrosterone (DHEA)-SO

    Penning, Trevor M

    Vitamins and hormones

    2018  Volume 108, Page(s) 309–331

    Abstract: Dehydroepiandrosterone (DHEA)- ... ...

    Abstract Dehydroepiandrosterone (DHEA)-SO
    MeSH term(s) Antineoplastic Agents/pharmacology ; Dehydroepiandrosterone Sulfate/administration & dosage ; Dehydroepiandrosterone Sulfate/metabolism ; Dehydroepiandrosterone Sulfate/therapeutic use ; Delayed-Action Preparations ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Steroid 17-alpha-Hydroxylase/antagonists & inhibitors
    Chemical Substances Antineoplastic Agents ; Delayed-Action Preparations ; Dehydroepiandrosterone Sulfate (57B09Q7FJR) ; CYP17A1 protein, human (EC 1.14.14.19) ; Steroid 17-alpha-Hydroxylase (EC 1.14.14.19)
    Language English
    Publishing date 2018-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 201161-x
    ISSN 2162-2620 ; 0083-6729
    ISSN (online) 2162-2620
    ISSN 0083-6729
    DOI 10.1016/bs.vh.2018.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: AKR1C3 (type 5 17β-hydroxysteroid dehydrogenase/prostaglandin F synthase): Roles in malignancy and endocrine disorders.

    Penning, Trevor M

    Molecular and cellular endocrinology

    2018  Volume 489, Page(s) 82–91

    Abstract: Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) ... ...

    Abstract Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F
    MeSH term(s) Aldo-Keto Reductase Family 1 Member C3/antagonists & inhibitors ; Aldo-Keto Reductase Family 1 Member C3/chemistry ; Aldo-Keto Reductase Family 1 Member C3/genetics ; Aldo-Keto Reductase Family 1 Member C3/metabolism ; Endocrine Gland Neoplasms/enzymology ; Endocrine Gland Neoplasms/genetics ; Endocrine System Diseases/enzymology ; Endocrine System Diseases/genetics ; Enzyme Inhibitors/pharmacology ; Epigenesis, Genetic/drug effects ; Humans ; Steroids/biosynthesis
    Chemical Substances Enzyme Inhibitors ; Steroids ; Aldo-Keto Reductase Family 1 Member C3 (EC 1.1.1.357)
    Language English
    Publishing date 2018-09-19
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 187438-x
    ISSN 1872-8057 ; 0303-7207
    ISSN (online) 1872-8057
    ISSN 0303-7207
    DOI 10.1016/j.mce.2018.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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