Hazlehurst, J. M., Oprescu, A. I., Nikolaou, N. et al. (11 more authors) (2016) Dual-5α-Reductase Inhibition Promotes Hepatic Lipid Accumulation in Man. The Journal of Clinical Endocrinology & Metabolism, 101 (1). pp. 103-113. ISSN 0021-972X
Abstract
Context: 5α-Reductase 1 and 2 (SRD5A1, SRD5A2) inactivate cortisol to 5α-dihydrocortisol in addition to their role in the generation of DHT. Dutasteride (dual SRD5A1 and SRD5A2 inhibitor) and finasteride (selective SRD5A2 inhibitor) are commonly prescribed, but their potential metabolic effects have only recently been identified. Objective: Our objective was to provide a detailed assessment of the metabolic effects of SRD5A inhibition and in particular the impact on hepatic lipid metabolism. Design: We conducted a randomized study in 12 healthy male volunteers with detailed metabolic phenotyping performed before and after a 3-week treatment with finasteride (5 mg od) or dutasteride (0.5 mg od). Hepatic magnetic resonance spectroscopy (MRS) and two-step hyperinsulinemic euglycemic clamps incorporating stable isotopes with concomitant adipose tissue microdialysis were used to evaluate carbohydrate and lipid flux. Analysis of the serum metabolome was performed using ultra-HPLC-mass spectrometry. Setting: The study was performed in the Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, United Kingdom. Main Outcome Measure: Incorporation of hepatic lipid was measured with MRS. Results: Dutasteride, not finasteride, increased hepatic insulin resistance. Intrahepatic lipid increased on MRS after dutasteride treatment and was associated with increased rates of de novo lipogenesis. Adipose tissue lipid mobilization was decreased by dutasteride. Analysis of the serum metabolome demonstrated that in the fasted state, dutasteride had a significant effect on lipid metabolism. Conclusions: Dual-SRD5A inhibition with dutasteride is associated with increased intrahepatic lipid accumulation. - See more at: http://press.endocrine.org/doi/10.1210/jc.2015-2928#sthash.KmmY91Iw.dpuf
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Endocrine Society. This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s) - See more at: http://press.endocrine.org/doi/10.1210/jc.2015-2928#sthash.KmmY91Iw.dpuf |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Nov 2016 16:11 |
Last Modified: | 21 Nov 2016 16:11 |
Published Version: | http://dx.doi.org/10.1210/jc.2015-2928 |
Status: | Published |
Publisher: | Endocrine Society |
Identification Number: | 10.1210/jc.2015-2928 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107955 |