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首页> 外文期刊>American Journal of Physiology >Multihormonal regulation of hepatic sinusoidal Ntcp gene expression.
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Multihormonal regulation of hepatic sinusoidal Ntcp gene expression.

机译：肝窦性Ntcp基因表达的多激素调节。

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摘要

Bile acids are efficiently removed from sinusoidal blood by a number of transporters including the Na+-taurocholate-cotransporting polypeptide (Ntcp). Na+-dependent bile salt uptake, as well as Ntcp, are expressed twofold higher in male compared with female rat livers. Also, estrogen administration to male rats decreases Ntcp expression. The aims of this study were to determine the hormonal mechanism(s) responsible for this sexually dimorphic expression of Ntcp. We examined castrated and hypophysectomized rats of both sexes. Sex steroid hormones, growth hormone, thyroid, and glucocorticoids were administered, and livers were examined for changes in Ntcp messenger RNA (mRNA). Ntcp mRNA and protein content were selectively increased in males. Estradiol selectively decreased Ntcp expression in males, whereas ovariectomy increased Ntcp in females, confirming the importance of estrogens in regulating Ntcp. Hypophysectomy decreased Ntcp mRNA levels in males and prevented estrogen administration from decreasing Ntcp, indicating the importance of pituitary hormones. Although constant infusion of growth hormone to intact males reduced Ntcp, its replacement alone after hypophysectomy did not restore the sex differences. In contrast, thyroid hormone and corticosterone increased Ntcp mRNA in hypophysectomized rats. Sex differences in Ntcp mRNA levels were produced only when the female pattern of growth hormone was administered to animals also receiving thyroid and corticosterone. Thyroid and dexamethasone also increased Ntcp mRNA in isolated rat hepatocytes, whereas growth hormone decreased Ntcp. These findings demonstrate the essential role that pituitary hormones play in the sexually dimorphic control of Ntcp expression in adult rat liver and in the mediation of estrogen effects.
机译：胆汁酸可以通过包括Na +-牛磺胆酸盐共转运多肽（Ntcp）在内的许多转运蛋白从正弦血液中有效去除。与雌性大鼠肝脏相比，雄性中Na +依赖性胆汁盐的摄取以及Ntcp的表达高出两倍。而且，雌激素给予雄性大鼠降低了Ntcp表达。这项研究的目的是确定导致这种Ntcp性二态表达的激素机制。我们检查了cast割和hypo割的雌雄大鼠。服用了性类固醇激素，生长激素，甲状腺和糖皮质激素，并检查了肝脏中Ntcp Messenger RNA（mRNA）的变化。男性中Ntcp mRNA和蛋白质含量选择性增加。雌二醇选择性降低男性的Ntcp表达，而卵巢切除术增加女性的Ntcp，证实了雌激素在调节Ntcp中的重要性。垂体切除术降低了男性中的Ntcp mRNA水平，并阻止了雌激素给药使Ntcp降低，表明垂体激素的重要性。尽管不断向完整的男性输注生长激素会降低Ntcp，但仅在垂体后叶切除术替代其并不能恢复性别差异。相比之下，垂体切除术大鼠的甲状腺激素和皮质酮增加了Ntcp mRNA的表达。 Ntcp mRNA水平上的性别差异仅在将雌性生长激素施用于同样接受甲状腺和皮质酮的动物时才会产生。甲状腺和地塞米松也增加了离体大鼠肝细胞中的Ntcp mRNA，而生长激素则降低了Ntcp。这些发现证明垂体激素在成年大鼠肝脏中Ntcp表达的性二态性控制和雌激素作用的介导中起着重要作用。

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