ArticleThe Journal of clinical endocrinology and metabolism2017
AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome.
Article in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05979389 (Pilot Trial of Bicalutamide Versus Placebo in Reproductive-Aged Women With Nonalcoholic Fatty Liver Disease), which is not on this map. Cited by 139 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Pilot Trial of Bicalutamide Versus Placebo in Reproductive-Aged Women With Nonalcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovary Syndrome (PCOS)
Who cites it
139 citing papers in PubMed, 3 syntheses or guidelines pooled it, 195 citations in OpenAlex.
- Society for Endocrinology Clinical Practice Guideline for the Evaluation of Androgen Excess in Women.Clinical endocrinology · 2025Guideline
- Premature adrenarche and metabolic risk: a systematic review and meta-analysis.European journal of endocrinology · 2025Pooled it
- Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies.Molecular metabolism · 2020Pooled it
- Hepatic metabolism of 11-oxygenated androgens in humans: an integrated in vivo and ex vivo approach.European journal of endocrinology · 2025Trial
- Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis.Drugs in R&D · 2023Trial
- Novel aldo-keto reductase 1C3 inhibitor affects androgen metabolism but not ovarian function in healthy women: a phase 1 study.European journal of endocrinology · 2023Trial
- Randomized clinical trial: effect of low-dose flutamide on abdominal adipogenic function in normal-weight women with polycystic ovary syndrome.Fertility and sterility · 2023Trial
- MASLD, diabetes and PMOS across the female life stages.Diabetologia · 2026Review
- Neuroendocrine regulation of adipose partitioning in polyendocrine metabolic ovarian syndrome: the gut-brain-adipose axis.Journal of endocrinological investigation · 2026Review
- From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.Stem cell reviews and reports · 2026Review
- Redox biology in PCOS: Biomarkers, mechanistic networks, and targeted interventions (Review).International journal of molecular medicine · 2026Review
- Potential Mechanisms Linking Excessive Testosterone to PMOS: Insights from Network Toxicology and Machine Learning.Metabolites · 2026Article
- Polyendocrine metabolic ovarian syndrome in pregnancy: pathophysiology and outcomes.Nature reviews. Endocrinology · 2026Review
- Accurate Measurement of Serum Free Testosterone Levels via Liquid Chromatography‒Tandem Mass Spectrometry (LC‒MS/MS) has Predictive Value in the Diagnosis of Polycystic Ovary Syndrome and Associated Metabolic Disorders.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- AKR1C3 inhibitors and exploiters for the treatment and therapeutic monitoring of cancer: a patent review (2020-present).Expert opinion on therapeutic patents · 2026Review
- Maternal exposure to biosolids reshapes chemical burden and steroidogenic pathways to promote adipogenic differentiation in a sheep model.Environment international · 2026Article
- Polyendocrine metabolic ovarian syndrome (PMOS)/polycystic ovary syndrome (PCOS): current and future trends.The Journal of clinical investigation · 2026Review
- Molecular Mechanisms Underlying Reproductive Dysfunction in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Bridging the Practice Gap: Polycystic Ovary Syndrome as an Under-Recognised Risk State for Ischaemic Stroke and Cardiovascular Disease.Journal of clinical medicine · 2026Review
- A case control study of subjective sleep characteristics and polycystic ovary syndrome.Scientific reports · 2026Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS. Methods: We performed a human deep metabolic in vivo phenotyping study examining the systemic and intra-adipose effects of acute and chronic androgen exposure in 10 PCOS women, in comparison with 10 body mass index-matched healthy controls, complemented by in vitro experiments. Results: PCOS women had increased intra-adipose concentrations of testosterone (P = 0.0006) and dihydrotestosterone (P = 0.01), with increased expression of the androgen-activating enzyme aldo-ketoreductase type 1 C3 (AKR1C3) (P = 0.04) in subcutaneous adipose tissue. Adipose glycerol levels in subcutaneous adipose tissue microdialysate supported in vivo suppression of lipolysis after acute androgen exposure in PCOS (P = 0.04). Mirroring this, nontargeted serum metabolomics revealed prolipogenic effects of androgens in PCOS women only. In vitro studies showed that insulin increased adipose AKR1C3 expression and activity, whereas androgen exposure increased adipocyte de novo lipid synthesis. Pharmacologic AKR1C3 inhibition in vitro decreased de novo lipogenesis. Conclusions: These findings define an intra-adipose mechanism of androgen activation that contributes to adipose remodeling and a systemic lipotoxic metabolome, with intra-adipose androgens driving lipid accumulation and insulin resistance in PCOS. AKR1C3 represents a promising therapeutic target in PCOS.
Indexed as
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.