Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1
Vitamin A (retinol) is important for multiple functions in mammals. In testis, the role of vitamin A in the regulation of testicular functions is clearly involved in rodents. It is essential for sperm production. Vitamin A deficiency adversely affects testosterone secretion. Adult Leydig cells are r...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00644/full |
| _version_ | 1828340171370659840 |
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| author | Yan Yang Yan Yang Jiao Luo Dan Yu Tiantian Zhang Qilian Lin Quan Li Xupeng Wu Zhijian Su Qihao Zhang Qi Xiang Qi Xiang Yadong Huang Yadong Huang |
| author_facet | Yan Yang Yan Yang Jiao Luo Dan Yu Tiantian Zhang Qilian Lin Quan Li Xupeng Wu Zhijian Su Qihao Zhang Qi Xiang Qi Xiang Yadong Huang Yadong Huang |
| author_sort | Yan Yang |
| collection | DOAJ |
| description | Vitamin A (retinol) is important for multiple functions in mammals. In testis, the role of vitamin A in the regulation of testicular functions is clearly involved in rodents. It is essential for sperm production. Vitamin A deficiency adversely affects testosterone secretion. Adult Leydig cells are responsible for testosterone production in male. The role of vitamin A in regulating the differentiation of Leydig cells is still unknown. In this study, we explored the roles and underlying mechanisms of vitamin A in Leydig cell differentiation. We found that vitamin A could regulate the Leydig cells differentiation. Leydig cell differentiation is adversely affected in mice maintained on a vitamin A-free diet. This effect is mediated by alcohol dehydrogenase 1 (ADH1). ADH1 could increase retinoic acid (RA) synthesis, then RA facilitates Leydig cell differentiation by activating the steroidogenic factor 1 gene (Nr5a1) promoter activity, which consequently promotes Leydig cell specific gene expression, resulting in progenitor Leydig cells differentiation into functional Leydig cells. This is the first study connecting a metabolic enzyme of retinol (ADH1) to the the regulation of Leydig cell differentiation, which will provide experimental evidence for the development of therapeutics to promote Leydig regeneration through the administration of a RA signaling regulator or a vitamin A supplement. |
| first_indexed | 2024-04-13T22:52:56Z |
| format | Article |
| id | doaj.art-5acaf1d476dc487fb1b66380ab164c1b |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T22:52:56Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-5acaf1d476dc487fb1b66380ab164c1b2022-12-22T02:26:07ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-10-01910.3389/fendo.2018.00644414328Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1Yan Yang0Yan Yang1Jiao Luo2Dan Yu3Tiantian Zhang4Qilian Lin5Quan Li6Xupeng Wu7Zhijian Su8Qihao Zhang9Qi Xiang10Qi Xiang11Yadong Huang12Yadong Huang13Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaDepartment of Biomedical Engineering, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, Jinan University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou, ChinaDepartment of Pharmacology, Jinan University, Guangzhou, ChinaVitamin A (retinol) is important for multiple functions in mammals. In testis, the role of vitamin A in the regulation of testicular functions is clearly involved in rodents. It is essential for sperm production. Vitamin A deficiency adversely affects testosterone secretion. Adult Leydig cells are responsible for testosterone production in male. The role of vitamin A in regulating the differentiation of Leydig cells is still unknown. In this study, we explored the roles and underlying mechanisms of vitamin A in Leydig cell differentiation. We found that vitamin A could regulate the Leydig cells differentiation. Leydig cell differentiation is adversely affected in mice maintained on a vitamin A-free diet. This effect is mediated by alcohol dehydrogenase 1 (ADH1). ADH1 could increase retinoic acid (RA) synthesis, then RA facilitates Leydig cell differentiation by activating the steroidogenic factor 1 gene (Nr5a1) promoter activity, which consequently promotes Leydig cell specific gene expression, resulting in progenitor Leydig cells differentiation into functional Leydig cells. This is the first study connecting a metabolic enzyme of retinol (ADH1) to the the regulation of Leydig cell differentiation, which will provide experimental evidence for the development of therapeutics to promote Leydig regeneration through the administration of a RA signaling regulator or a vitamin A supplement.https://www.frontiersin.org/article/10.3389/fendo.2018.00644/fullvitamin ALeydig celldifferentiationalcohol dehydrogenase 1retinoic acidsteroidogenic factor 1 |
| spellingShingle | Yan Yang Yan Yang Jiao Luo Dan Yu Tiantian Zhang Qilian Lin Quan Li Xupeng Wu Zhijian Su Qihao Zhang Qi Xiang Qi Xiang Yadong Huang Yadong Huang Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 Frontiers in Endocrinology vitamin A Leydig cell differentiation alcohol dehydrogenase 1 retinoic acid steroidogenic factor 1 |
| title | Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 |
| title_full | Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 |
| title_fullStr | Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 |
| title_full_unstemmed | Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 |
| title_short | Vitamin A Promotes Leydig Cell Differentiation via Alcohol Dehydrogenase 1 |
| title_sort | vitamin a promotes leydig cell differentiation via alcohol dehydrogenase 1 |
| topic | vitamin A Leydig cell differentiation alcohol dehydrogenase 1 retinoic acid steroidogenic factor 1 |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00644/full |
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