Tam S P, Archer T K, Deeley R G
Proc Natl Acad Sci U S A. 1986 May;83(10):3111-5. doi: 10.1073/pnas.83.10.3111.
Treatment of HepG2 cells with various concentrations of 17 beta-estradiol has revealed two distinct thresholds for induction of different apolipoproteins. Maximal increases in apolipoprotein AI and CII (apoAI and apoCII) secretion can be obtained with initial concentrations of hormone of 20 nM or greater, while a similar induction of apoB and apoE requires in excess of 500 nM. Both responses involve alterations in the concentrations of apolipoprotein mRNAs. Analyses of the kinetics of accumulation of the apolipoproteins in response to high concentrations of hormone indicate that induction of apoB and apoE occurs coordinately, but it lags behind that of apoAI and apoCII by 5-6 hr. This lag can be eliminated by preexposing the cells to low concentrations of hormone. The ability to induce apoAI and apoCII and the kinetics with which they respond to low levels of estrogen correlate with levels of nuclear type I estrogen binding sites, while increases in apoE and apoB synthesis in response to high concentrations of hormone correlate with the induction of type II sites. Testosterone alone has no effect on the rates of apolipoprotein secretion, but it does increase the concentration of estrogen required to maximally induce apoCII and apoAI by a mechanism that involves high-affinity androgen receptors. This effect may be attributable to the testosterone-dependent induction of a cytoplasmic moderate-affinity estrogen-binding component.
用不同浓度的17β-雌二醇处理HepG2细胞，发现诱导不同载脂蛋白有两个不同的阈值。初始激素浓度为20 nM或更高时，载脂蛋白AI和CII（apoAI和apoCII）分泌可达到最大增加，而类似地诱导apoB和apoE则需要超过500 nM。两种反应都涉及载脂蛋白mRNA浓度的改变。对高浓度激素刺激下载脂蛋白积累动力学的分析表明，apoB和apoE的诱导是协同发生的，但比apoAI和apoCII滞后5 - 6小时。通过使细胞预先暴露于低浓度激素可消除这种滞后现象。诱导apoAI和apoCII的能力以及它们对低水平雌激素反应的动力学与核I型雌激素结合位点的水平相关，而高浓度激素刺激下apoE和apoB合成的增加与II型位点的诱导相关。单独的睾酮对载脂蛋白分泌速率没有影响，但它确实通过一种涉及高亲和力雄激素受体的机制增加了最大诱导apoCII和apoAI所需的雌激素浓度。这种作用可能归因于睾酮依赖性诱导的一种细胞质中等亲和力雌激素结合成分。
