Ohtani R, Yayama K, Takano M, Itoh N, Okamoto H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Endocrinology. 1992 Mar;130(3):1331-8. doi: 10.1210/endo.130.3.1311238.
The effects of hormones and cytokines on angiotensinogen production were studied in primary cultured rat hepatocytes. The basal secretion of angiotensinogen decreased during culture. The addition of dexamethasone and (Bu)2cAMP completely prevented this decrease. Angiotensinogen secretion by freshly plated hepatocytes was slightly increased in response to dexamethasone, but after 24 h in culture, hepatocytes no longer responded to dexamethasone alone. When hepatocytes were treated with (Bu)2cAMP, glucagon, or forskolin, angiotensinogen secretion increased in response to dexamethasone in a concentration-dependent manner. 17 beta-Estradiol and T3 failed to stimulate angiotensinogen secretion in either the presence or absence of (Bu)2cAMP. Interleukin-6 (IL-6) exhibited a stimulatory activity on angiotensinogen secretion, which was dependent on the presence of dexamethasone, whereas IL-1 and tumor necrosis factor had no effect in either the presence or absence of dexamethasone and/or (Bu)2cAMP. Unlike primary cultured hepatocytes, angiotensinogen secretion by rat hepatoma H4IIEC3 cells increased in response to dexamethasone alone. This increase was not enhanced by (Bu)2cAMP, but was enhanced by IL-6. Thus, in primary cultures of rat hepatocytes, neither glucocorticoid, cAMP, nor IL-6 alone stimulated angiotensinogen production, but a combination of glucocorticoid and cAMP or of glucocorticoid and IL-6 exhibited a stimulatory activity on angiotensinogen production. These results suggest that angiotensinogen production in the liver is synergistically regulated by these factors, whereas the hepatoma cell line H4IIEC3 lacks the regulatory mechanism of cAMP on glucocorticoid-induced angiotensinogen production.
在原代培养的大鼠肝细胞中研究了激素和细胞因子对血管紧张素原产生的影响。培养过程中血管紧张素原的基础分泌减少。地塞米松和（Bu）2cAMP的添加完全阻止了这种减少。新鲜接种的肝细胞对血管紧张素原的分泌因地塞米松而略有增加，但培养24小时后，肝细胞不再单独对地塞米松产生反应。当用（Bu）2cAMP、胰高血糖素或福斯可林处理肝细胞时，血管紧张素原的分泌以浓度依赖的方式因地塞米松而增加。无论有无（Bu）2cAMP，17β-雌二醇和T3均未能刺激血管紧张素原的分泌。白细胞介素-6（IL-6）对血管紧张素原的分泌表现出刺激活性，这取决于地塞米松的存在，而IL-1和肿瘤坏死因子在地塞米松和/或（Bu）2cAMP存在或不存在的情况下均无作用。与原代培养的肝细胞不同，大鼠肝癌H4IIEC3细胞的血管紧张素原分泌仅对地塞米松有反应而增加。这种增加未被（Bu）2cAMP增强，但被IL-6增强。因此，在大鼠肝细胞的原代培养中，糖皮质激素、cAMP或单独的IL-6均未刺激血管紧张素原的产生，但糖皮质激素和cAMP或糖皮质激素和IL-6的组合对血管紧张素原的产生表现出刺激活性。这些结果表明，肝脏中血管紧张素原的产生受这些因素的协同调节，而肝癌细胞系H4IIEC3缺乏cAMP对糖皮质激素诱导的血管紧张素原产生的调节机制。
