Isabel Viola Wagner1,2,3, Iuliia Savchuk1, Lena Sahlin4, Alexandra Kulle5, Nora Klöting6,7, Arne Dietrich6, Paul-Martin Holterhus5, Jörg Dötsch2, Matthias Blüher6, Olle Söder1. 1. Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 2. Department of Pediatrics, Medical Faculty, University of Cologne, Cologne, Germany. 3. Department of Pediatrics, Medical Faculty, UKSH, University of Lübeck, Lübeck, Germany. 4. Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 5. Hormone Center for Pediatric Endocrinology Lab, University Hospital Kiel, Kiel, Germany. 6. Department of Medicine and Department of Surgery, Integrated Research and Treatment Center (IFB Adiposity Diseases), University of Leipzig, Leipzig, Germany. 7. Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Muenchen at the University of Leipzig, Leipzig, Germany.
Abstract
INTRODUCTION: Obesity in women is often associated with hyperandrogenism, but the role of adipose tissue (AT) in androgen synthesis remains unclear. Therefore, we studied whether AT could be a source of androgens promoting hyperandrogenism. METHODS: Subcutaneous and visceral (visc) AT was collected from lean and obese women. Androgen levels were evaluated in serum, AT, and cell-culture supernatant. Gene and protein expression of steroidogenic enzymes were determined. RESULTS: Obese subjects had elevated serum androgen levels, which reduced after weight loss. Androgens were measurable in AT and in cell-culture supernatants of adipocytes. Steroids were higher in AT from obese women, with the highest difference for testosterone in visc AT (+7.9-fold, p = 0.032). Steroidogenic enzymes were expressed in human AT with depot-specific differences. Obese women showed a significantly higher expression of genes of the backdoor pathway and of CYP19 in visc AT. CONCLUSION: The whole steroidogenic machinery of the classical and backdoor pathways of steroidogenesis, and the capacity for androgen biosynthesis, were found in both AT depots and cultured adipocytes. Therefore, we hypothesize that AT is a de novo site of androgen production and the backdoor pathway of steroidogenesis might be a new pathomechanism for hyperandrogenism in women with obesity.
INTRODUCTION: Obesity in women is often associated with hyperandrogenism, but the role of adipose tissue (AT) in androgen synthesis remains unclear. Therefore, we studied whether AT could be a source of androgens promoting hyperandrogenism. METHODS: Subcutaneous and visceral (visc) AT was collected from lean and obese women. Androgen levels were evaluated in serum, AT, and cell-culture supernatant. Gene and protein expression of steroidogenic enzymes were determined. RESULTS: Obese subjects had elevated serum androgen levels, which reduced after weight loss. Androgens were measurable in AT and in cell-culture supernatants of adipocytes. Steroids were higher in AT from obese women, with the highest difference for testosterone in visc AT (+7.9-fold, p = 0.032). Steroidogenic enzymes were expressed in human AT with depot-specific differences. Obese women showed a significantly higher expression of genes of the backdoor pathway and of CYP19 in visc AT. CONCLUSION: The whole steroidogenic machinery of the classical and backdoor pathways of steroidogenesis, and the capacity for androgen biosynthesis, were found in both AT depots and cultured adipocytes. Therefore, we hypothesize that AT is a de novo site of androgen production and the backdoor pathway of steroidogenesis might be a new pathomechanism for hyperandrogenism in women with obesity.
Authors: Christopher R McCartney; Christine M Burt Solorzano; James T Patrie; John C Marshall; Daniel J Haisenleder Journal: Steroids Date: 2018-09-12 Impact factor: 2.668
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