Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat.
Effects of hepatectomy, nephrectomy, and nephrectomy/uremia on the metabolism of parathyroid hormone in the rat.
复制标题
肝切除、肾切除和肾切除/尿毒症对大鼠甲状旁腺激素代谢的影响。
DOI：
10.1172/jci110052
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
PottsJr,JT
中科院分区：
文献类型：
--
作者：
Segre,GV;D'Amour,P;Hultman,A;PottsJr,JT
来自几个实验室的报告显示，广泛的肝脏提取循环甲状旁腺激素，导致我们检查了近全肝切除对激素代谢为循环片段的影响，以及对其从血浆中清除的影响。通过凝胶过滤、序列特异性放射免疫分析或Edman反应序列分析，检测125I标记和未标记牛甲状旁腺激素从血浆中的消失率，以及循环碎片的出现、消失和化学和免疫化学特征。将接受近全肝切除的清醒大鼠的结果与假治疗、肾切除和短期尿毒症大鼠(研究在肾切除后2d)的结果进行比较。与假手术组相比，其他各组大鼠清除~(125)I标记激素的速度均较慢，但以肝切除后最为明显，注射完整激素后，各时间点肝切除大鼠循环中的羧基末端片段浓度均较假手术组显著降低。对注射了~(125)I标记激素的大鼠血浆样品的序列分析表明，在假手术组、肾切除组和肾切除/尿毒症组大鼠血浆中，含有完整激素序列第34和37位氨基酸的羧基末端片段丰富，而在肝切除大鼠中检测不到。这些数据表明，由于体内肝脏产生了注射激素代谢所产生的大部分羧基末端片段，肝脏内特定的细胞类型一定是负责酶的主要部位(S)；因此，对体外分离的肝细胞的酶特性的研究很可能会产生与完整动物的激素代谢有关的生理信息。
Reports from several laboratories, showing extensive hepatic extraction of circulating parathyroid hormone, led us to examine the effect of near-total hepatectomy on the metabolism of the hormone to circulating fragments, and on its clearance from plasma. The rate of disappearance of125I-labeled and unlabeled bovine parathyroid hormone from plasma, and the appearance, disappearance, and chemical and immunochemical characteristics of circulating fragments were examined by gel filtration and either sequence-specific radioimmunoassays or sequence analysis using the Edman reaction. Results from awake rats subjected to near-total hepatectomy were compared with those found in sham-treated, nephrectomized, and short-term uremic rats (studied 2 d after nephrectomy). When compared with the sham-treated group, all other groups clear125I-labeled hormone more slowly; after hepatectomy, however, the clearance rate is most strikingly decreased.After injection of intact hormone, the concentration of carboxy-terminal fragments in the circulation of hepatectomized rats is greatly reduced at all time intervals when compared with that in sham-treated rats. Sequence analysis of plasma samples, collected from rats into which125I-labeled hormone had been injected, shows that carboxy-terminal fragments having positions 34 and 37 of the intact hormone sequence as their amino-terminal amino acids are abundant in sham-treated, nephrectomized, and nephrectomized/uremic rats, but are undetectable in hepatectomized rats. The data suggest that inasmuch as the liver in vivo generates most of the carboxy-terminal fragments resulting from the metabolism of injected hormone, specific cell types within the liver must be the principal locus of the responsible enzyme(s); thus, studies of the enzymic properties of isolated hepatic cells in vitro most likely will yield information of physiologic relevance to the metabolism of the hormone in the intact animal.