Hadley S P, Hoffmann W E, Kuhlenschmidt M S, Sanecki R K, Dorner J L
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana.
Enzyme. 1990;43(2):89-98. doi: 10.1159/000468711.
Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal liver morphology and increases in serum alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP) and by the appearance of an unusual isoenzyme of alkaline phosphatase known as the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been shown whether the increases in serum ALT, GGT, and LALP are as a result of an increase in production of these enzymes or as a result of the GC-induced hepatocellular swelling and possible membrane alterations. Also, it has been assumed that the mechanism of production of CALP is via GC-induced gene derepression and de novo protein synthesis; however, this hypothesis has not been directly tested. Using isolated dog hepatocytes maintained in a confluent monolayer culture in the presence and absence of GC or cyclic AMP, no statistical increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic AMP also caused no statistical increase in ALT and GGT; however, we demonstrate that these conditions clearly stimulated the de novo synthesis of LALP. These conditions do not induce the synthesis of CALP as determined by a sensitive immunoassay. The data obtained using this in vitro model suggest that the primary mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may be other than that of de novo protein synthesis. Likewise, in vitro production of CALP may be a mechanism more complex than the conditions tested in this study.
糖皮质激素（GC）诱导的犬肝病的特征是肝脏形态异常，血清丙氨酸氨基转移酶（ALT）、γ-谷氨酰转移酶（GGT）和肝脏碱性磷酸酶同工酶（LALP）升高，以及出现一种不寻常的碱性磷酸酶同工酶，即皮质类固醇诱导的碱性磷酸酶同工酶（CALP）。目前尚未表明血清ALT、GGT和LALP的升高是这些酶产生增加的结果，还是GC诱导的肝细胞肿胀和可能的膜改变的结果。此外，人们认为CALP的产生机制是通过GC诱导的基因去抑制和从头合成蛋白质；然而，这一假设尚未得到直接验证。在有或没有GC或环磷酸腺苷（cAMP）的情况下，使用在汇合单层培养中维持的分离犬肝细胞，未观察到血清ALT、GGT或LALP有统计学意义的增加。GC和cAMP的组合也未导致ALT和GGT有统计学意义的增加；然而，我们证明这些条件明显刺激了LALP的从头合成。通过灵敏的免疫测定确定，这些条件不会诱导CALP的合成。使用该体外模型获得的数据表明，GC处理的犬体内血清ALT和GGT升高的主要机制可能不是从头合成蛋白质。同样，CALP的体外产生可能是一种比本研究中测试的条件更复杂的机制。
