Abstract:
: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 hHDL(3) 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.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Lai WA,Yeh YT,Lee MT,Wu LS,Ke FC,Hwang JJdoi
10.1194/jlr.M030239subject
Has Abstractpub_date
2013-02-01 00:00:00pages
365-78issue
2eissn
0022-2275issn
1539-7262pii
jlr.M030239journal_volume
54pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Journal of lipid research
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doi:
更新日期:1999-08-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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更新日期:1968-01-01 00:00:00
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journal_title:Journal of lipid research
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