ArticleEndocrinology2022
Conversion of Classical and 11-Oxygenated Androgens by Insulin-Induced AKR1C3 in a Model of Human PCOS Adipocytes.
Article in Endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.Human reproduction update · 2024Pooled it
- 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
- Adrenal AKR1C3-mediated androgen activation contributes to hyperandrogenism in prepubertal ovariectomized rats.Translational pediatrics · 2026Article
- Adaptation and exploratory factor analysis of a PCOS-specific HRQoL questionnaire in a South Indian population.BMC women's health · 2026Article
- Characterization of an NADPH-dependent 17β-hydroxysteroid dehydrogenase from a urinary tract bacterial isolate.The Journal of steroid biochemistry and molecular biology · 2026Article
- 11-oxygenated androgens in healthy young adults: Does use of hormonal contraceptives matter? The Fit Futures Study.Journal of endocrinological investigation · 2026Article
- Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders.Andrology · 2026Review
- A case control study of subjective sleep characteristics and polycystic ovary syndrome.Scientific reports · 2026Article
- Development and Validation of a High-performance Liquid Chromatography-Tandem Mass Spectrometry Method for Detecting Adrenocortical Hormones and Establishment of Age-stratified Reference Intervals in Reproductive-aged Women from Guangxi, China.Annals of laboratory medicine · 2026Article
- Comprehensive analysis of the deleterious nonsynonymous, non-coding SNPs and cancer variants of human aldo-keto reductase type 1 (AKR1C1) protein and their probable association with disease risk and progression: a computational study.Biochemistry and biophysics reports · 2026Article
- The Ontogeny of Distinct Reproductive Phenotypes in Girls at Risk for PCOS During the Postmenarchal Transition.The Journal of clinical endocrinology and metabolism · 2026Article
- Nutrients and bioactive compounds in polycystic ovary syndrome: updated insights into effects and underlying mechanisms.Frontiers in nutrition · 2026Review
- On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2025Review
- 11-Oxygenated Androgens Inhibit Brown Adipose Tissue Differentiation.Endocrinology · 2025Article
- Relations of Insulin Resistance, Body Weight, Vitamin D Deficiency, SHBG and Androgen Levels in PCOS Patients.Biomedicines · 2025Article
- Radioactive Tracing of Testosterone Reveals Minimal Formation of 5α-DHT in SGBS Cells and Human Primary Adipocytes.Journal of the Endocrine Society · 2025Article
- POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: The significance of functional adrenal hyperandrogenism in polycystic ovary syndrome across the lifespan.Reproduction (Cambridge, England) · 2025Review
- An expanded metabolic pathway for androgen production by commensal bacteria.Nature microbiology · 2025Article
- Specific and potent inhibition of steroid hormone pre-receptor regulator AKR1C2 by perfluorooctanoic acid: Implications for androgen metabolism.The Journal of steroid biochemistry and molecular biology · 2025Article
- Machine learning combined multi-omics analysis to explore key oxidative stress features in systemic lupus erythematosus.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women. A common symptom of PCOS is hyperandrogenism (AE); however, the source of these androgens is uncertain. Aldo-keto reductase family 1 member C3 (AKR1C3) catalyzes the formation of testosterone (T) and 5α-dihydrotestosterone (DHT) in peripheral tissues, which activate the androgen receptor (AR). AKR1C3 is induced by insulin in adipocytes and may be central in driving the AE in PCOS. We elucidated the conversion of both classical and 11-oxygenated androgens to potent androgens in a model of PCOS adipocytes. Using high-performance liquid chromatography (HPLC) discontinuous kinetic assays to measure product formation by recombinant AKR1C3, we found that the conversion of 11-keto-Δ4-androstene-3,17-dione (11K-4AD) to 11-ketotestosterone (11K-T) and 11-keto-5α-androstane-3,17-dione (11K-5AD) to 11-keto-5α-dihydrotestosterone (11K-DHT) were superior to the formation of T and DHT. We utilized a stable isotope dilution liquid chromatography high resolution mass spectrometric (SID-LC-HRMS) assay for the quantification of both classical and 11-oxygenated androgens in differentiated Simpson-Golabi-Behmel syndrome adipocytes in which AKR1C3 was induced by insulin. Adipocytes were treated with adrenal derived 11β-hydroxy-Δ4-androstene-3,17-dione (11β-OH-4AD), 11K-4AD, or Δ4-androstene-3,17-dione (4AD). The conversion of 11β-OH-4AD and 11K-4AD to 11K-T required AKR1C3. We also found that once 11K-T is formed, it is inactivated to 11β-hydroxy-testosterone (11β-OH-T) by 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1). Our data reveal a unique role for HSD11B1 in protecting the AR from AE. We conclude that the 11-oxygenated androgens formed in adipocytes may contribute to the hyperandrogenic profile of PCOS women and that AKR1C3 is a potential therapeutic target to mitigate the AE of PCOS.
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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.