biostudies-literature00480Dumesic DANational Center for Advancing Translational SciencesEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSNCATS NIH HHSEndocrine Technologies Support CoreNational Institutes of HealthNIH HHSbvab158https://www.ebi.ac.uk/biostudies/studies/S-EPMC8513761biostudies-literatureUnknown5(11)<h4>Context</h4>Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women.<h4>Objective</h4>This work examines whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women.<h4>Methods</h4>This prospective cohort study took place in an academic center and comprised 19 normal-weight PCOS women and 21 age- and body mass index-matched controls. Interventions included circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. Serum T/A4 ratios, hormone/metabolic measures, and <i>AKR1C3</i> expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si).<h4>Results</h4>Increased serum T/A4 ratios (<i>P</i> = .040) and log adipose-IR values (<i>P</i> = .002) in PCOS women vs controls were accompanied by <i>AKR1C3</i> messenger RNA overexpression of PCOS adipocytes matured in vitro (<i>P</i> = .016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TGs: R = -0.65, <i>P</i> = .002) and the TG index (R<i> </i>= -0.57, <i>P</i> = .011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R = -0.57, <i>P</i> = .013) and TG index (R = -0.50, <i>P</i> = .036), respectively, without significant relationships with other metabolic measures.<h4>Conclusion</h4>An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.Journal of the Endocrine SocietySerum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women.PMC8513761P50 HD071836UL1TR001881UL1 TR001881P51ODO11092P50HD071836P51 OD011092Abbott DHChazenbalk GDLu GNaik RDumesic DATulberg AMcNamara MGrogan TR48falseSerum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women.<h4>Context</h4>Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women.<h4>Objective</h4>This work examines whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women.<h4>Methods</h4>This prospective cohort study took place in an academic center and comprised 19 normal-weight PCOS women and 21 age- and body mass index-matched controls. Interventions included circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. Serum T/A4 ratios, hormone/metabolic measures, and <i>AKR1C3</i> expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si).<h4>Results</h4>Increased serum T/A4 ratios (<i>P</i> = .040) and log adipose-IR values (<i>P</i> = .002) in PCOS women vs controls were accompanied by <i>AKR1C3</i> messenger RNA overexpression of PCOS adipocytes matured in vitro (<i>P</i> = .016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TGs: R = -0.65, <i>P</i> = .002) and the TG index (R<i> </i>= -0.57, <i>P</i> = .011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R = -0.57, <i>P</i> = .013) and TG index (R = -0.50, <i>P</i> = .036), respectively, without significant relationships with other metabolic measures.<h4>Conclusion</h4>An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.2021-01-01T00:00:00Z2021 Nov2024-11-12T13:18:38.679Z2022-02-11T12:43:29.105ZS-EPMC85137613466103910.1210/jendso/bvab158