ArticleThe Journal of clinical endocrinology and metabolism2022
Excess 11-Oxygenated Androgens in Women With Severe Insulin Resistance Are Mediated by Adrenal Insulin Receptor Signaling.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Society for Endocrinology Clinical Practice Guideline for the Evaluation of Androgen Excess in Women.Clinical endocrinology · 2025Guideline
- The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.Journal of proteome research · 2025Pooled it
- The Expression of Placental 17β-Hydroxysteroid Dehydrogenase Genes Is Associated with the Elevation of Active Androgens and Estrogens in Pregnant Women, but Does Not Affect 11-Oxygenated C19 Steroids.International journal of molecular sciences · 2026Article
- Current insights into monitoring of congenital adrenal hyperplasia.Frontiers in endocrinology · 2026Review
- 11-Oxygenated Androgens Inhibit Brown Adipose Tissue Differentiation.Endocrinology · 2025Article
- Stimulated Hyperinsulinemia Is Independently Associated with Higher Serum DHEAS in PCOS: A Retrospective Study.Journal of clinical medicine · 2025Article
- POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: The significance of functional adrenal hyperandrogenism in polycystic ovary syndrome across the lifespan.Reproduction (Cambridge, England) · 2025Review
- Research progress on the pathogenesis, clinical impact, and traditional Chinese medicine treatment of polycystic ovary syndrome complicated by insulin resistance.Frontiers in pharmacology · 2025Review
- Multi-omics elucidation ofFrontiers in nutrition · 2025Article
- Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study.Acta diabetologica · 2024Article
- Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome.Journal of the Endocrine Society · 2023Article
- Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome.Frontiers in endocrinology · 2023Review
- Androgen excess: a hallmark of polycystic ovary syndrome.Frontiers in endocrinology · 2023Review
- Insulin Resistance and Adrenal Androgen Synthesis Viewed Through a Monogenic Lens.The Journal of clinical endocrinology and metabolism · 2022Article
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7 authors at 3 institutions in 1 country.
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Abstract
contextSyndromes of severe insulin resistance (SIR) include insulin receptoropathy, in which all signaling downstream of the insulin receptor is lost, and lipodystrophy, in which some signaling pathways are impaired and others preserved. Women with SIR commonly have ovarian hyperandrogenemia; adrenal-derived 11-oxygenated androgens, produced by CYP11B1, have not been studied.
objectiveWe aimed to evaluate classic pathway androgens (androstenedione, testosterone) and 11-oxygenated androgens in women with SIR and hyperandrogenemia, and to elucidate the role of insulin receptor signaling for 11-oxygenated androgen production by comparing lipodystrophy and receptoropathy.
methodsSteroid hormones were quantified using LC-MS/MS in a cross-sectional study of 18 women with hyperandrogenemia and SIR (11 lipodystrophy, 7 receptoropathy) and 23 controls. To assess ovarian vs adrenal origin, steroids were compared in receptoropathy patients with (Ovary+) vs without (Ovary-) ovarian function.
resultsCompared with controls, classic androgens were elevated in both lipodystrophy and receptoropathy, and 11-oxygenated androgens were increased in lipodystrophy (2.9-fold higher 11β-hydroxyandrostenedione (11OHA4), 2.4-fold higher 11-ketoandrostenedione (11KA4), 3.6-fold higher 11-ketotestosterone (11KT); P < 0.01), but not receptoropathy. Product-to-precursor ratios for CYP11B1 conversion of androstenedione to 11OHA4 were similar in lipodystrophy and controls but decreased in receptoropathy (6.5-fold lower than control; P = 0.001). Classic androgens were elevated in Ovary + but not Ovary- patients.
conclusions11-Oxygenated androgens are elevated in lipodystrophy but not receptoropathy. In SIR, insulin receptor signaling is necessary for adrenal hyperandrogenemia but not ovarian hyperandrogenemia; excess classic androgens are derived from the ovaries. Insulin receptor signaling increases adrenal 19-carbon steroid production, which may have implications for more common disorders of mild IR.
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