Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor
Obesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity i...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.868572/full |
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| author | Mingxiao Feng Sara Divall Dustin Jones Vaibhave Ubba Xiaomin Fu Xiaomin Fu Ling Yang Hong Wang Xiaofeng Yang Sheng Wu Sheng Wu |
| author_facet | Mingxiao Feng Sara Divall Dustin Jones Vaibhave Ubba Xiaomin Fu Xiaomin Fu Ling Yang Hong Wang Xiaofeng Yang Sheng Wu Sheng Wu |
| author_sort | Mingxiao Feng |
| collection | DOAJ |
| description | Obesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity in female mice, and conditional knock-out of the androgen receptor (Ar) in the liver (LivARKO) protects female mice from DHT-induced glucose intolerance and hyperinsulinemia. Since altered metabolic function will regulate reproduction, and liver plays a pivotal role in the reversible regulation of reproductive function, we sought to determine the reproductive phenotype of LivARKO mice under normal and hyperandrogenemic conditions. Using Cre/Lox technology, we deleted the Ar in the liver, and we observed LivARKO female mice have normal puberty timing, cyclicity and reproductive function. After DHT treatment, like control mice, LivARKO experience altered estrous cycling, reduced numbers of corpus lutea, and infertility. Liver Ar is not involved in hyperandrogenemia-induced reproductive dysfunction. The reproductive dysfunction in the DHT-treated LivARKO lean females with normal glucose homeostasis indicates that androgen-induced reproductive dysfunction is independent from metabolic dysfunction. |
| first_indexed | 2024-12-11T16:16:54Z |
| format | Article |
| id | doaj.art-433ff166b7e3428eb40c306fb79e81d7 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-11T16:16:54Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-433ff166b7e3428eb40c306fb79e81d72022-12-22T00:58:56ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.868572868572Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen ReceptorMingxiao Feng0Sara Divall1Dustin Jones2Vaibhave Ubba3Xiaomin Fu4Xiaomin Fu5Ling Yang6Hong Wang7Xiaofeng Yang8Sheng Wu9Sheng Wu10Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Pediatrics, Seattle’s Children’s Hospital, University of Washington, Seattle, WA, United StatesDepartment of Cellular and Molecular Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Cardiovascular Sciences/Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United StatesDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaMedical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, PA, United StatesDepartment of Cardiovascular Sciences/Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United StatesDepartment of Cardiovascular Sciences/Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United StatesDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Cardiovascular Sciences/Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, United StatesObesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity in female mice, and conditional knock-out of the androgen receptor (Ar) in the liver (LivARKO) protects female mice from DHT-induced glucose intolerance and hyperinsulinemia. Since altered metabolic function will regulate reproduction, and liver plays a pivotal role in the reversible regulation of reproductive function, we sought to determine the reproductive phenotype of LivARKO mice under normal and hyperandrogenemic conditions. Using Cre/Lox technology, we deleted the Ar in the liver, and we observed LivARKO female mice have normal puberty timing, cyclicity and reproductive function. After DHT treatment, like control mice, LivARKO experience altered estrous cycling, reduced numbers of corpus lutea, and infertility. Liver Ar is not involved in hyperandrogenemia-induced reproductive dysfunction. The reproductive dysfunction in the DHT-treated LivARKO lean females with normal glucose homeostasis indicates that androgen-induced reproductive dysfunction is independent from metabolic dysfunction.https://www.frontiersin.org/articles/10.3389/fendo.2022.868572/fullPCOS: polycystic ovary syndromeDHTdihydrotestosteroneandrogen receptor (AR)liverpuberty |
| spellingShingle | Mingxiao Feng Sara Divall Dustin Jones Vaibhave Ubba Xiaomin Fu Xiaomin Fu Ling Yang Hong Wang Xiaofeng Yang Sheng Wu Sheng Wu Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor Frontiers in Endocrinology PCOS: polycystic ovary syndrome DHT dihydrotestosterone androgen receptor (AR) liver puberty |
| title | Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor |
| title_full | Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor |
| title_fullStr | Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor |
| title_full_unstemmed | Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor |
| title_short | Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor |
| title_sort | comparison of reproductive function between normal and hyperandrogenemia conditions in female mice with deletion of hepatic androgen receptor |
| topic | PCOS: polycystic ovary syndrome DHT dihydrotestosterone androgen receptor (AR) liver puberty |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.868572/full |
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