Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells.
Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells.
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DOI：
10.1073/pnas.88.6.2375
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发表时间：
1991-03
影响因子：
11.1
通讯作者：
M. Reyland;John T. Gwynne;Patricia Forgez;M. Prack;David L. Williams
中科院分区：
文献类型：
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作者：
M. Reyland;John T. Gwynne;Patricia Forgez;M. Prack;David L. Williams
脂质转运蛋白载脂蛋白E （apoE）在体内的许多外周组织中表达，包括肾上腺和睾丸。为了研究载脂蛋白e在肾上腺胆固醇稳态中的作用，我们在Y1小鼠肾上腺皮质细胞系中表达了一个人类载脂蛋白e基因组克隆。Y1细胞不表达内源性apoE mRNA或蛋白。在Y1细胞中表达apoE导致基底甾体生成的显著减少；与Y1亲本细胞相比，荧光类固醇的分泌减少了7- 100倍以上。添加5-胆固醇-3 β，25-二醇未能克服这些细胞中类固醇生成的抑制。通过胆固醇[14C]油酸酯的产生来测量，在基础条件下胆固醇酯化在Y1亲本和转染apoe的细胞系中是相似的。与促肾上腺皮质激素或二丁基cAMP孵育后，Y1亲本细胞中胆固醇[14C]油酸酯的产生减少了5倍，但在转染apoe的细胞系中没有变化。这些结果表明apoE可能是肾上腺细胞胆固醇利用和类固醇生成的重要调节剂。
The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, we have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to greater than 100-fold relative to Y1 parent cells. Addition of 5-cholesten-3 beta,25-diol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells.