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  • 标题:An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17α-hydroxylase, C17–20 lyase
  • 本地全文:下载
  • 作者:Gongqiao Zhang ; Linda K. Curtiss ; Randy L. Wade
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:1998
  • 卷号:39
  • 期号:12
  • 页码:2406-2414
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Ovarian theca/interstitial cells produce androgens in response to luteinizing hormone (LH) stimulation and apolipoprotein (apo) E exerts a selective effect on the type of steroid product made by these cells. We have identified an apoE synthetic peptide containing the low density lipoprotein (LDL) receptor binding domain, acetyl-Y(LRK LRKRLLRDADDL)2C, that mimics the activity of native apoE. Depending on the concentration, the apoE synthetic peptide either enhanced or inhibited the LH-stimulated production of androstenedione with concomitant changes in the mRNA for its synthetic enzyme, P450 17α-hydroxylase, C17–20 lyase, without any changes in progesterone production or the mRNA for its synthetic enzyme, P450 cholesterol side-chain cleavage. The apoE synthetic peptide caused changes in the rate of transcription of the mRNA for P450 17α-hydroxylase, C17–20 lyase without altering its stability. Pretreatment of the theca/interstitial cells with receptor-associated protein, which blocks apoE binding to members of the LDL receptor superfamily, prevented the apoE synthetic peptide-mediated stimulation of androstenedione and mRNA for P450 17α-hydroxylase, C17–20 lyase, but did not attenuate the inhibitory activity of the peptide. Thus, apolipoprotein E selectively altered the type of steroid made by ovarian theca/interstitial cells by regulating the transcription of mRNA for the gene for P450 17α-hydroxylase, C17–20 lyase, in part through its interaction with apolipoprotein E-specific receptors of the LDL receptor superfamily. —Zhang, G., L. K. Curtiss, R. L. Wade, and C. A. Dyer. An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17α-hydroxylase, C17–20 lyase. J. Lipid Res. 1998. 39: 2406–2414.
  • 关键词:androgen ; RT-PCR ; P450 cholesterol side-chain cleavage ; receptor-associated protein ; LDL receptor superfamily ; steroidogenesis
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