VDR mediated HSD3B1 to regulate lipid metabolism and promoted testosterone synthesis in mouse Leydig cells

Xue Zhen; Zhuang Jianan; Bai Hao; Wang Ling; Lu Hongzhao; Wang Shanshan; Zeng Wenxian; Zhang Tao

doi:10.1007/s13258-022-01232-1

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자료유형: 학술저널

저자정보: Xue Zhen (Shaanxi University of Technology China) Zhuang Jianan (Shaanxi University of Technology China) Bai Hao (Shaanxi University of Technology China) Wang Ling (Shaanxi University of Technology China) Lu Hongzhao (Shaanxi University of Technology China) Wang Shanshan (Shaanxi University of Technology China) Zeng Wenxian (Shaanxi University of Technology China) Zhang Tao (Shaanxi University of Technology China)

저널정보: 한국유전학회 Genes & Genomics Genes & Genomics Vol.44 No.5

발행연도: 2022.5

수록면: 583 - 592 (10page)

DOI: 10.1007/s13258-022-01232-1

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Background The vitamin D receptor (VDR) mediates the pleiotropic biological actions that include osteoporosis, immune responses and androgen synthesis wherein the VDR transcriptionally regulates expression of the genes involved in this complex process. 3β-Hydroxysteroid dehydrogenase-1 (HSD3B1) is an absolutely necessary enzyme for androgen synthesis. Objective The purpose of the present study was to explore the molecular mechanism of VDR mediated HSD3B1 regulation of lipid metabolism and testosterone synthesis. Methods The levels of VDR, HSD3B1 and lipid metabolism associated protein were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blot. The levels of testosterone concentrations in cell culture media serum by enzyme-linked immunosorbent assay (ELISA). Targeted relationship between VDR and Hsd3b1 was evaluated by dual-luciferase reporter assay. Results Based on the data analysis of mouse testicular proteome, we found that the expression of HSD3B1 was significantly reduced after VDR deletion. Here, we identified that Hsd3b1 was widely expressed in different tissues of mice by RT-qPCR, and was highly expressed in testis, and mainly located in testicular Leydig cells. Dual-luciferase assay confirmed that VDR could bind candidate vitamin D responsive elements (VDREs) in upstream region of Hsd3b1, and enhance gene expression. Furthermore, over-expression VDR and HSD3B1 significantly increased testosterone synthesis in mice Leydig cells. Meanwhile, Lpl expression was significantly down-regulated and Angptl4 expression was significantly up-regulated in the present of HSD3B1 overexpression. Both LPL and ANGPTL4 play important roles in regulating lipid metabolism. Conclusions The present study unveiled VDR mediated HSD3B1 to regulate lipid metabolism and promoted testosterone synthesis in mouse Leydig cells. These findings will greatly help us to understand the roles of VDR and HSD3B1 in testosterone synthesis and lipid metabolism.

Background The vitamin D receptor (VDR) mediates the pleiotropic biological actions that include osteoporosis, immune responses and androgen synthesis wherein the VDR transcriptionally regulates expression of the genes involved in this complex process. 3β-Hydroxysteroid dehydrogenase-1 (HSD3B1) is an absolutely necessary enzyme for androgen synthesis. Objective The purpose of the present study was to explore the molecular mechanism of VDR mediated HSD3B1 regulation of lipid metabolism and testosterone synthesis. Methods The levels of VDR, HSD3B1 and lipid metabolism associated protein were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blot. The levels of testosterone concentrations in cell culture media serum by enzyme-linked immunosorbent assay (ELISA). Targeted relationship between VDR and Hsd3b1 was evaluated by dual-luciferase reporter assay. Results Based on the data analysis of mouse testicular proteome, we found that the expression of HSD3B1 was significantly reduced after VDR deletion. Here, we identified that Hsd3b1 was widely expressed in different tissues of mice by RT-qPCR, and was highly expressed in testis, and mainly located in testicular Leydig cells. Dual-luciferase assay confirmed that VDR could bind candidate vitamin D responsive elements (VDREs) in upstream region of Hsd3b1, and enhance gene expression. Furthermore, over-expression VDR and HSD3B1 significantly increased testosterone synthesis in mice Leydig cells. Meanwhile, Lpl expression was significantly down-regulated and Angptl4 expression was significantly up-regulated in the present of HSD3B1 overexpression. Both LPL and ANGPTL4 play important roles in regulating lipid metabolism. Conclusions The present study unveiled VDR mediated HSD3B1 to regulate lipid metabolism and promoted testosterone synthesis in mouse Leydig cells. These findings will greatly help us to understand the roles of VDR and HSD3B1 in testosterone synthesis and lipid metabolism.

#HSD3B1 · VDR · Leydig cells · Testosterone synthesis · Lipid metabolism

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