SFEBES2025 Oral Communications Reproductive and Neuroendocrinology (6 abstracts)
Changes in 11-oxygenated androgen metabolism after bariatric surgery in patients with obesity are mediated by downregulation of aldoketoreductase type 1C3 (AKR1C3) activity
Clare Miller 1,2 , Talal Saad Almukhlifi 3,4 , Tara McDonnell 1,2 , Leanne Cussen 1,2 , Angela E. Taylor 5 , Marie McIlroy 1 , Jean O’Connell 3,6 , Donal O’Shea 3,6 , Helen Heneghan 3,6 , Wiebke Arlt 7,8 , Karl Heinz-Storbeck 8,9 , Mark Sherlock 1,2 & Michael W. O’Reilly 1,2
1Androgens in Health and Disease Research Group, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 2Department of Endocrinology, Beaumont Hospital, Dublin, Ireland; 3Department of Bariatric Surgery, St Vincent’s University Hospital, Dublin, Ireland; 4Department of Surgery, Prince Sattam Bin Abdulaziz University, Al-Kharj City, Saudi Arabia; 5Steroid Metabolomics Analysis Core (SMAC), Department of Metabolism and Systems Science, University of Birmingham, Birmingham, United Kingdom; 6Weight Management Services, St Columcilles Hospital, Loughlinstown, Dublin, Ireland; 7Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; 8Medical Research Council Laboratory of Medical Sciences, London, United Kingdom; 9Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa
The circulating androgen pool is comprised of classic androgens and those derived from the 11-oxygenated pathway. Aldoketoreductase type 1C3 (AKR1C3), which activates androstenedione (A4) to testosterone (T) in the classic pathway and 11-ketoandrostenedione (11KA4) to 11-ketotestosterone (11KT) in the 11-oxygenated pathway, is highly expressed in adipose tissue. Expression is increased in obesity and serum 11KT levels correlate with body mass index. Here we hypothesised that weight loss induced by bariatric surgery impacts on 11-oxygenated androgen metabolism by reducing expression of AKR1C3 in adipose tissue. Multisteroid profiling of serum and 24-hour urine samples by liquid chromatography tandem mass spectrometry was performed pre and postoperatively in patients undergoing bariatric surgery. Baseline anthropometric and metabolic data were collected before and after surgery. A total of 60 patients were included [n=40 female; median BMI 49.3 (IQR 45.1-54.6) kg/m2; median age 50.5 (IQR 43.3-56.6) years]. Median % weight loss was 17.6 (IQR 13.7-21.2)% at a median of 18.0 (IQR 16.8-20.3) weeks postoperatively. Weight loss resulted in a significant reduction in serum levels of A4 (P<0.05) in women, while dehydroepiandrosterone and T increased significantly in men (P<0.05 for each). Urinary (5αTHF+THF)/THE, a marker of systemic 11b-hydroxysteroid dehydrogenase type 1 activity, was not significantly altered by weight loss. Serum levels of 11β-hydroxyandrostenedione, 11KA4 and 11β-hydroxytestoterone did not change significantly after bariatric surgery. In contrast, serum levels of 11KT decreased significantly [1.5 (IQR 1.0-2.7) vs 1.3 (IQR 0.87-1.8), P<0.05)]. The ratio of serum 11KT/11KA4, a surrogate marker of AKR1C3 activity, also reduced significantly postoperatively (P<0.05). This is the first in vivo study to demonstrate the impact of bariatric surgery on 11-oxygenated androgen metabolism. Reduced serum levels of the active 11-oxygenated androgen 11KT reflect lower AKR1C3 activity in adipose tissue. Our data reinforce the critical links between obesity and perturbations in androgen metabolism in men and women.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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