Ovarian granulosa cells utilize scavenger receptor SR-BI to evade cellular cholesterol homeostatic control for steroid synthesis
| Autor: | Ferng Chun Ke, Ming-Ting Lee, Yi-Ting Yeh, Jiuan Jiuan Hwang, Wei-An Lai, Leang-Shin Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
CD36 Antigens
medicine.medical_specialty Intracellular Space Receptors Cytoplasmic and Nuclear QD415-436 Biology Biochemistry Rats Sprague-Dawley Transforming Growth Factor beta1 liver receptor homolog-1 chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Homeostasis Humans Scavenger receptor follicle-stimulating hormone Research Articles Granulosa Cells transforming growth factor β1 Cholesterol Liver receptor homolog-1 LDL receptor Cell Biology SCARB1 Sterol Sterol regulatory element-binding protein Rats Protein Transport chemistry Gene Expression Regulation Receptors LDL scavenger receptor class B member I Female Steroids lipids (amino acids peptides and proteins) Sterol regulatory element-binding protein 2 Follicle Stimulating Hormone sterol regulatory element-binding protein Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Journal of Lipid Research, Vol 54, Iss 2, Pp 365-378 (2013) |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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