Tosh D, Alberti K G, Agius L
Department of Medicine, University of Newcastle upon Tyne, U.K.
Biochem J. 1989 May 15;260(1):183-7. doi: 10.1042/bj2600183.
The biochemical and functional heterogeneity of hepatocytes in different zones of the liver acinus may be related to the concentrations of hormones within the liver acinus. We examined the effects of hypophysectomy, which causes marked changes in plasma hormone levels and in activities of hepatic enzymes that are normally heterogeneously distributed, on the degree of metabolic zonation within the liver acinus. In hypophysectomized rats the activity of alanine aminotransferase was increased, but its normal zonation (predominance in the periportal zone) was preserved. The activity in cultured periportal and perivenous hepatocytes was increased by dexamethasone, but not by glucagon. Periportal hepatocytes from hypophysectomized rats expressed higher rates of gluconeogenesis in culture than did perivenous hepatocytes, irrespective of the absence or presence of dexamethasone, glucagon or insulin. Similar differences in rates of ketogenesis and in the mitochondrial redox state in response to glucagon were observed between periportal and perivenous hepatocytes from hypophysectomized rats as between cell populations from normal rats. Although hypophysectomy causes marked changes in hepatic enzyme activities, it does not alter the degree of zonation of alanine aminotransferase, gluconeogenesis or the mitochondrial redox state within the liver acinus.
肝腺泡不同区域肝细胞的生化和功能异质性可能与肝腺泡内激素的浓度有关。我们研究了垂体切除对肝腺泡内代谢分区程度的影响,垂体切除会导致血浆激素水平以及通常呈非均匀分布的肝酶活性发生显著变化。在垂体切除的大鼠中,丙氨酸转氨酶的活性增加,但其正常分区(在门静脉周围区域占优势)得以保留。地塞米松可增加培养的门静脉周围和肝静脉周围肝细胞的活性,但胰高血糖素无此作用。无论是否存在地塞米松、胰高血糖素或胰岛素,垂体切除大鼠的门静脉周围肝细胞在培养中比肝静脉周围肝细胞表现出更高的糖异生速率。在垂体切除大鼠的门静脉周围和肝静脉周围肝细胞之间,观察到的酮生成速率和线粒体氧化还原状态对胰高血糖素反应的差异,与正常大鼠的细胞群体之间的差异相似。虽然垂体切除会导致肝酶活性发生显著变化,但它不会改变肝腺泡内丙氨酸转氨酶的分区程度、糖异生或线粒体氧化还原状态。