Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis
Cellular cholesterol is known to be under homeostatic control in nonsteroidogenic cells, and this intrigued us to understand how such control works in steroidogenic cells that additionally use cholesterol for steroid hormone synthesis. We employed primary culture of rat ovarian granulosa cells to st...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520428020 |
| _version_ | 1818386415380070400 |
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| author | Wei-An Lai (賴薇安) Yi-Ting Yeh (葉伊婷) Ming-Ting Lee (李明亭) Leang-Shin Wu (吳兩新) Ferng-Chun Ke (柯逢春) Jiuan-Jiuan Hwang (黃娟娟 |
| author_facet | Wei-An Lai (賴薇安) Yi-Ting Yeh (葉伊婷) Ming-Ting Lee (李明亭) Leang-Shin Wu (吳兩新) Ferng-Chun Ke (柯逢春) Jiuan-Jiuan Hwang (黃娟娟 |
| author_sort | Wei-An Lai (賴薇安) |
| collection | DOAJ |
| description | Cellular cholesterol is known to be under homeostatic control in nonsteroidogenic cells, and this intrigued us to understand how such control works in steroidogenic cells that additionally use cholesterol for steroid hormone synthesis. We employed primary culture of rat ovarian granulosa cells to study how steroidogenic cells adapt to acquire sufficient cholesterol to meet the demand of active steroidogenesis under the stimulation of gonadotropin follicle-stimulating hormone (FSH) and cytokine transforming growth factor (TGF)β1. We found that TGFβ1 potentiated FSH to upregulate scavenger receptor class B member I (SR-BI) and LDL receptor (LDLR), both functional in uptaking cholesterol as hHDL3 and hLDL supplementation enhanced progesterone production, and the effect of each lipoprotein was completely or partially blocked by SR-BI selective inhibitor BLT-1. Uptaken cholesterol could also be stored in lipid droplets. Importantly, LDLR and SR-BI responded to sterol with different sensitivity. Giving cells lipoproteins or 25-hydroxycholesterol downregulated Ldlr but not Scarb1; Scarb1 was ultimately downregulated by excessive sterol accumulation under 25-hydroxycholesterol and aminoglutethimide (inhibitor of steroidogenesis) cotreatment. Furthermore, transcription factors sterol regulatory element-binding protein (SREBP)-2 and liver receptor homolog (LRH)-1 crucially mediated Ldlr and Scarb1 differential response to sterol challenge. This study reveals that ovarian granulosa cells retain the cholesterol homeostatic control machinery like nonsteroidogenic cells, although during active steroidogenesis, they utilize SR-BI to evade such feedback control. |
| first_indexed | 2024-12-14T03:53:41Z |
| format | Article |
| id | doaj.art-282020d114414681accfdd96231fca26 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:53:41Z |
| publishDate | 2013-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-282020d114414681accfdd96231fca262022-12-21T23:18:09ZengElsevierJournal of Lipid Research0022-22752013-02-01542365378Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesisWei-An Lai (賴薇安)0Yi-Ting Yeh (葉伊婷)1Ming-Ting Lee (李明亭)2Leang-Shin Wu (吳兩新)3Ferng-Chun Ke (柯逢春)4Jiuan-Jiuan Hwang (黃娟娟5Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Physiology, School of Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei, Taiwan; andDepartment of Animal Science and Technology, College of Bio-Resources and Agriculture, Taipei, TaiwanTo whom correspondence should be addressed. (F-C.K.) fck@ccms.ntu.edu.tw; Institute of Molecular and Cellular Biology, College of Life Science, National Taiwan University, Taipei, Taiwan; To whom correspondence should be addressed. (J-J.H.) jiuanh@ym.edu.twTo whom correspondence should be addressed. (J-J.H.) jiuanh@ym.edu.tw; Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; To whom correspondence should be addressed. (J-J.H.) jiuanh@ym.edu.twCellular cholesterol is known to be under homeostatic control in nonsteroidogenic cells, and this intrigued us to understand how such control works in steroidogenic cells that additionally use cholesterol for steroid hormone synthesis. We employed primary culture of rat ovarian granulosa cells to study how steroidogenic cells adapt to acquire sufficient cholesterol to meet the demand of active steroidogenesis under the stimulation of gonadotropin follicle-stimulating hormone (FSH) and cytokine transforming growth factor (TGF)β1. We found that TGFβ1 potentiated FSH to upregulate scavenger receptor class B member I (SR-BI) and LDL receptor (LDLR), both functional in uptaking cholesterol as hHDL3 and hLDL supplementation enhanced progesterone production, and the effect of each lipoprotein was completely or partially blocked by SR-BI selective inhibitor BLT-1. Uptaken cholesterol could also be stored in lipid droplets. Importantly, LDLR and SR-BI responded to sterol with different sensitivity. Giving cells lipoproteins or 25-hydroxycholesterol downregulated Ldlr but not Scarb1; Scarb1 was ultimately downregulated by excessive sterol accumulation under 25-hydroxycholesterol and aminoglutethimide (inhibitor of steroidogenesis) cotreatment. Furthermore, transcription factors sterol regulatory element-binding protein (SREBP)-2 and liver receptor homolog (LRH)-1 crucially mediated Ldlr and Scarb1 differential response to sterol challenge. This study reveals that ovarian granulosa cells retain the cholesterol homeostatic control machinery like nonsteroidogenic cells, although during active steroidogenesis, they utilize SR-BI to evade such feedback control.http://www.sciencedirect.com/science/article/pii/S0022227520428020scavenger receptor class B member ILDL receptorsterol regulatory element-binding proteinliver receptor homolog-1follicle-stimulating hormonetransforming growth factor β1 |
| spellingShingle | Wei-An Lai (賴薇安) Yi-Ting Yeh (葉伊婷) Ming-Ting Lee (李明亭) Leang-Shin Wu (吳兩新) Ferng-Chun Ke (柯逢春) Jiuan-Jiuan Hwang (黃娟娟 Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis Journal of Lipid Research scavenger receptor class B member I LDL receptor sterol regulatory element-binding protein liver receptor homolog-1 follicle-stimulating hormone transforming growth factor β1 |
| title | Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis |
| title_full | Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis |
| title_fullStr | Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis |
| title_full_unstemmed | Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis |
| title_short | Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis |
| title_sort | ovarian granulosa cells utilize scavenger receptor sr bi to evade cellular cholesterol homeostatic control for steroid synthesis |
| topic | scavenger receptor class B member I LDL receptor sterol regulatory element-binding protein liver receptor homolog-1 follicle-stimulating hormone transforming growth factor β1 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520428020 |
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