In vivo bioactivities and clearance patterns of highly purified human luteinizing hormone isoforms
In vivo bioactivities and clearance patterns of highly purified human luteinizing hormone isoforms
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DOI：
10.1210/en.137.11.4827
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发表时间：
1996-11-01
期刊：
影响因子：
4.8
通讯作者：
Robertson, DM
中科院分区：
文献类型：
--
作者：
Burgon, PG;Stanton, PG;Robertson, DM
先前的研究表明，高纯度的人垂体促黄体生成素亚型在体外表现出20倍的生物活性。这项研究的目的是确定相应的血浆半衰期、代谢清除率(MCR)和这些人(H)黄体生成素亚型的体内生物活性。造模后的成年雄性大鼠静脉注射HLH异构体。注射。对于半衰期研究，然后在6小时内连续采集血液，并使用特定的免疫荧光分析法检测血清中的HLH。所有HLH(n=19)亚型均呈双指数消失型，A组分的初始快半衰期(t1/2)为12.8±-3.7min，其次为慢组分B，t1/2为58.9+/-4.4min。当B组分与A组分的唾液酸含量相关时，B组分相对于A组分的患病率显著增加(r=0.81P<；0.001)。类似地，最大尿流率与唾液酸含量呈显著正相关(r=0.77，P&0.001)。然后对两个T1/2分量的基础进行了研究。在第一个实验中，大鼠在给药90min后采集主要含有B组分的血浆，然后注射到第二只动物体内，只观察到B组分，而没有发现A组分，这表明这两个T1/2组分不是HLH亚型在体内各室间重新分布的产物。在第二个实验中，发现B组分依赖于唾液酸含量，因为所需的HLH亚型迅速消失(t1/2=8.6+/-3.1)，B组分的比例下降到
Previous studies have shown that highly purified isoforms of human pituitary LH exhibited a 20-fold range of in vitro bioactivities. The aim of this study was to determine the corresponding plasma half-lives, metabolic clearance rates (MCR), and in vivo bioactivities of these human (h) LH isoforms. Cannulated adult male rats were administered hLH isoforms as a bolus i.v. injection. For the half-life studies, blood was then serially collected over a 6-h period, and serum was assayed for hLH using a specific immunofluorometric assay. All hLH (n = 19) isoforms exhibited biexponential disappearance profiles with an initial fast half-life (t1/2) for component A of 12.8 +/- 3.7 min, followed by a slow component B with t1/2 of 58.9 +/- 4.4 min. The prevalence of component B in relation to component A increased significantly (r = 0.81, P < 0.001) over a 3-fold range when correlated with the sialic acid content of the isoform. Similarly, the MCR showed a significant correlation (r = 0.77, P < 0.001) with sialic acid content. The basis for the two t1/2 components was then investigated. In the first experiment, rat plasma containing primarily component B was collected 90 min after hLH isoform administration and injected into a second animal Only component B was observed with no evidence of component A, which indicates that the two t1/2 components are not the product of the redistribution of the hLH isoform between body compartments. In the second experiment, component B was found to be dependent on sialic acid content, as desialylated hLH isoforms showed a rapid disappearance (t1/2 = 8.6 +/- 3.1) with the component B proportion decreasing to