Excess androgen production in subcutaneous adipose tissue of women with polycystic ovarian syndrome

Amer, Saad A.; Alzanati, Nadia G.; Warren, Avril; Tarbox, Rebecca; Khan, Raheela

Abstract

© 2019 Society for Endocrinology Published by Bioscientifica Ltd. The purpose of this study was to investigate androgen production and the role of insulin and LH in its regulation in subcutaneous adipose tissue (SAT) of women with polycystic ovarian syndrome (PCOS). Protein and mRNA expression of androgen synthesis enzymes (cytochrome P450 17A1 (CYP17A1) and aldo-keto reductase 1C3 (AKR1C3)) were measured in SAT biopsies from women with PCOS, diagnosed according to the Rotterdam criteria (n = 15) and healthy controls (n = 15). Cultured mature adipocytes (differentiated from SAT biopsies) were treated with insulin ± phosphoinositol-3-kinase inhibitor (LY294002) or LH ± insulin. CYP17A1 and AKR1C3 mRNA expression and testosterone concentrations were measured in treated and untreated adipocyte cultures. AKR1C3 mRNA was significantly (P < 0.001) greater in PCOS vs non-PCOS SAT, but CYP17A1 was not significantly different between the two groups. AKR1C3 and CYP17A1 protein expression was not significantly different in PCOS vs non-PCOS SAT. In untreated adipocyte cultures, CYP17A1, AKR1C3 and testosterone levels were significantly higher in the PCOS vs the non-PCOS groups. Addition of insulin increased AKR1C3 mRNA and testosterone levels, but not CYP17A1 mRNA in non-PCOS with no effect on PCOS adipocytes. The stimulatory effects of insulin were not inhibited by LY294002. Addition of LH increased CYP17A1, AKR1C3 and testosterone in non-PCOS adipocytes with no effect in PCOS adipocytes. In conclusion, SAT of women with PCOS produces excess androgen, which may contribute to PCOS-related hyperandrogenaemia. This SAT androgen excess is independent of obesity and is not directly stimulated by inulin or LH.

Citation

Amer, S. A., Alzanati, N. G., Warren, A., Tarbox, R., & Khan, R. (2019). Excess androgen production in subcutaneous adipose tissue of women with polycystic ovarian syndrome. Journal of Endocrinology, 241(1), 99-109. https://doi.org/10.1530/JOE-18-0674

• Journal Article Type: Article
• Acceptance Date: Feb 25, 2019
• Online Publication Date: Feb 1, 2019
• Publication Date: Feb 1, 2019
• Deposit Date: Mar 8, 2019
• Publicly Available Date: Feb 2, 2020
• Journal: Journal of Endocrinology
• Print ISSN: 0022-0795
• Electronic ISSN: 1479-6805
• Publisher: BioScientifica
• Peer Reviewed: Peer Reviewed
• Volume: 241
• Issue: 1
• Pages: 99-109
• DOI: https://doi.org/10.1530/JOE-18-0674
• Keywords: Polycystic ovarian syndrome, Adipose tissue, Hyperandrogenism, CYP17A1, AKR1C3, Hyperinsulinaemia
• Public URL: https://nottingham-repository.worktribe.com/output/1614436
• Publisher URL: https://joe.bioscientifica.com/view/journals/joe/aop/joe-18-0674.xml
• Additional Information: This manuscript has been accepted for publication in Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at 10.1530/JOE-18-0674 2019.
• Contract Date: Mar 8, 2019