ArticleThe Journal of steroid biochemistry and molecular biology2019
AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells.
Article in The Journal of steroid biochemistry and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Bone marrow-derived mesenchymal stem cell ameliorates post-stroke enterobacterial translocation through liver-gut axis.Stroke and vascular neurology · 2025Article
- In Vitro Analysis of AKR1D1 Interactions with Clopidogrel: Effects on Enzyme Activity and Gene Expression.Balkan journal of medical genetics : BJMG · 2024Article
- 5β-Dihydrosteroids: Formation and Properties.International journal of molecular sciences · 2024Review
- Novel Functionalized Spiro [Indoline-3,5'-pyrroline]-2,2'dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential.International journal of molecular sciences · 2023Article
- Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.International journal of molecular sciences · 2023Article
- The role of 11-oxygenated androgens in prostate cancer.Endocrine oncology (Bristol, England) · 2023Review
- A bile acid-related prognostic signature in hepatocellular carcinoma.Scientific reports · 2022Article
- Article
- AKR1D1 knockout mice develop a sex-dependent metabolic phenotype.The Journal of endocrinology · 2022Article
- Differential activity and expression of human 5β-reductase (AKR1D1) splice variants.Journal of molecular endocrinology · 2021Article
- Article
- Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo.The Journal of endocrinology · 2020Article
- AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease.Metabolism: clinical and experimental · 2019Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Steroid hormones, including glucocorticoids and androgens, have potent actions to regulate many cellular processes within the liver. The steroid A-ring reductase, 5β-reductase (AKR1D1), is predominantly expressed in the liver, where it inactivates steroid hormones and, in addition, plays a crucial role in bile acid synthesis. However, the precise functional role of AKR1D1 to regulate steroid hormone action in vitro has not been demonstrated. We have therefore hypothesised that genetic manipulation of AKR1D1 has the potential to regulate glucocorticoid availability and action in human hepatocytes. In both liver (HepG2) and non-liver cell (HEK293) lines, AKR1D1 over-expression increased glucocorticoid clearance with a concomitant decrease in the activation of the glucocorticoid receptor and the down-stream expression of glucocorticoid target genes. Conversely, knockdown of AKR1D1 using siRNA decreased glucocorticoid clearance and reduced the generation of 5β-reduced metabolites. In addition, the two 5α-reductase inhibitors finasteride and dutasteride failed to effectively inhibit AKR1D1 activity in either cell-free or hepatocellular systems. Through manipulation of AKR1D1 expression and activity, we have demonstrated its potent ability to regulate glucocorticoid availability and receptor activation within human hepatoma cells. These data suggest that AKR1D1 may have an important role in regulating endogenous (and potentially exogenous) glucocorticoid action that may be of particular relevance to physiological and pathophysiological processes affecting the liver.
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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.