Prenatal androgen excess impairs beta-cell function by decreased sirtuin 3 expression

in Journal of Endocrinology
Authors:
Yu Zhou Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Min Gong Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Yingfei Lu Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Jianquan Chen Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Rong Ju Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

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Correspondence should be addressed to J Chen or R Ju: jqchen68@hotmail.com or jurong@njmu.edu.cn
DOI:
https://doi.org/10.1530/JOE-21-0129
Volume/Issue:
Volume 251: Issue 1
Article Type:
Research Article
Page Range:
69–81
Online Publication Date:
03 Sep 2021
Copyright:
© Society for Endocrinology 2021
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Prenatal androgen exposure induces metabolic disorders in female offspring. However, the long-term effect of maternal testosterone excess on glucose metabolism, especially on pancreatic beta-cell function, is rarely investigated. Our current study mainly focused on the effects of prenatal testosterone exposure on glucose metabolism and pancreatic beta- cell function in aged female offspring. By using maternal mice and their female offspring as animal models, we found that prenatal androgen treatment induced obesity and glucose intolerance in aged offspring. These influences were accompanied by decreased fasting serum insulin concentration, elevated serum triglyceride, and testosterone concentrations. Glucose stimulated insulin secretion in pancreatic beta cells of aged female offspring was also affected by prenatal testosterone exposure. We further confirmed that increased serum testosterone contributed to downregulation of sirtuin 3 expression, activated oxidative stress, and impaired pancreatic beta-cell function in aged female offspring. Moreover, over-expression of sirtuin 3 in islets isolated from female offspring treated with prenatal testosterone normalized the oxidative stress level, restored cyclic AMP, and ATP generation, which finally improved glucose-stimulated insulin secretion in beta cells. Taken together, these results demonstrated that prenatal testosterone exposure caused a metabolic disturbance in aged female offspring via suppression of sirtuin 3 expression and activation of oxidative stress in pancreatic beta cells.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© Society for Endocrinology 2021
Page(s):
13
Article Type:
Research Article
Received Date:
27 Jul 2021
Accepted Date:
06 Aug 2021
Print Publication Date:
01 Oct 2021
Online Publication Date:
03 Sep 2021
Keywords:
prenatal androgen excess; beta cell function; aging; Sirt3; oxidative stress

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