Abstract
The scavenger receptor class B type I (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells and plays an important role in the reverse uptake of cholesterol to the liver and in the delivery of substrates for steroidogenesis in steroidogenic organs. We report here on the isolation and characterization of the upstream promoter region of the rat SR-BI gene. The transcription start site for rat SR-BI was mapped, and DNA sequence analysis revealed the presence of binding sites for the Sp1 family in the proximal 5'-flanking region. Analysis of deletion mutants with different 5' lengths revealed that the region between -121 and -90 base pairs from the transcription start site is essential for the efficient transcription of SR-BI. Both Sp1 and Sp3 bind to three GC boxes in the region (-141 to -1 base pairs) in a sequence-specific manner. Mutations in any of the GC boxes decreased efficient transcription from this promoter in MA-10 mouse Leydig tumor cells. The overexpression of Sp1 or Sp3 protein enhanced the rat SR-BI promoter activity. These results indicate that Sp1 family members of transcription factors are essential for transcription of the rat SR-BI gene.
Highlights
Steroidogenic tissue cells require cholesterol to support the synthesis of steroid hormones
Cholesterol, for steroidogenesis purposes, is preferentially supplied from circulating lipoproteins. Both low density lipoproteins (LDL)1 and high density lipoproteins (HDL) are capable of delivering cholesterol to support steroidogenesis, and the relative contributions of these two lipoproteins differ among species
scavenger receptor class B type I (SR-BI) is expressed in the steroidogenic organs and liver, which all display a selective uptake of HDL cholesterol ester [6, 11, 12]
Summary
The scavenger receptor class B type I (SR-BI) mediates the selective transport of lipids from high density lipoprotein to cells and plays an important role in the reverse uptake of cholesterol to the liver and in the delivery of substrates for steroidogenesis in steroidogenic organs. We and other investigators have shown that the expression of SR-BI mRNA in the immature rat ovary is rapidly induced in the theca interna cells by pregnant mare serum gonadotropin (PMSG) or human chorionic gonadotropin and that expression was observed in the corpus luteum of the adult rat ovary [11, 15] These observations support the conclusion that SR-BI serves as a selective mediator of cholesterol uptake for steroid hormone synthesis and plays an important role in female reproduction.
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