Evidence map›Paper›PMID 25974403›Full record

ArticleEndocrinology2015

5α-Reductase Type 2 Regulates Glucocorticoid Action and Metabolic Phenotype in Human Hepatocytes.

Maryam Nasiri, Nikolaos Nikolaou, Silvia Parajes, Nils P Krone, George Valsamakis, George Mastorakos, Beverly Hughes, Angela Taylor, Iwona J Bujalska, Laura L Gathercole and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  5. The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health.International journal of molecular sciences · 2022
    Review
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  11. Review
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  18. Article
  19. Article
  20. Intracrine androgen biosynthesis, metabolism and action revisited.Molecular and cellular endocrinology · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Maryam NasiriCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Nikolaos NikolaouCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Silvia ParajesCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Nils P KroneCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
George ValsamakisCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
George MastorakosCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Beverly HughesCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Angela TaylorCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Iwona J BujalskaCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Laura L GathercoleCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Jeremy W TomlinsonCentre for Endocrinology, Diabetes and Metabolism (M.N., S.P., N.P.K., B.H., A.T., I.J.B.), Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; Oxford Centre for Diabetes, Endocrinology & Metabolism (N.N., L.L.G., J.W.T.), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Endocrine Unit, Second Department of Obstetrics and Gynecology and Pathology Department (G.V., G.M.), Aretaieion University Hospital, Athens Medical School, Athens, 11528, Greece.
Oxford Centre for Diabetes, Endocrinology and Metabolism · GB

Funding

Medical Research Council G0802765
6 · The paper itself

Abstract

Glucocorticoids and androgens have both been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); androgen deficiency in males, androgen excess in females, and glucocorticoid excess in both sexes are associated with NAFLD. Glucocorticoid and androgen action are regulated at a prereceptor level by the enzyme 5α-reductase type 2 (SRD5A2), which inactivates glucocorticoids to their dihydrometabolites and converts T to DHT. We have therefore explored the role of androgens and glucocorticoids and their metabolism by SRD5A2 upon lipid homeostasis in human hepatocytes. In both primary human hepatocytes and human hepatoma cell lines, glucocorticoids decreased de novo lipogenesis in a dose-dependent manner. Whereas androgen treatment (T and DHT) increased lipogenesis in cell lines and in primary cultures of human hepatocytes from female donors, it was without effect in primary hepatocyte cultures from men. SRD5A2 overexpression reduced the effects of cortisol to suppress lipogenesis and this effect was lost following transfection with an inactive mutant construct. Conversely, pharmacological inhibition using the 5α-reductase inhibitors finasteride and dutasteride augmented cortisol action. We have demonstrated that manipulation of SRD5A2 activity can regulate lipogenesis in human hepatocytes in vitro. This may have significant clinical implications for those patients prescribed 5α-reductase inhibitors, in particular augmenting the actions of glucocorticoids to modulate hepatic lipid flux.

Indexed as

3-Oxo-5-alpha-Steroid 4-Dehydrogenase5-alpha Reductase InhibitorsAdultAgedAndrogensBiological TransportCells, CulturedFemaleFinasterideGlucocorticoidsHepatocytesHumansInsulinLipogenesisMaleMembrane Proteins3-Oxo-5-alpha-Steroid 4-Dehydrogenase5-alpha Reductase InhibitorsAndrogensFinasterideGlucocorticoidsInsulinMembrane ProteinsSRD5A2 protein, human

Identifiers

PMID25974403
PMCPMC4511138
OpenAlexW1845645347

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.