Canterbury J M, Bricker L A, Levey G S, Kozlovskis P L, Ruiz E, Zull J E, Reiss E
J Clin Invest. 1975 Jun;55(6):1245-53. doi: 10.1172/JCI108043.
The metabolism of bovine parathyroid hormone (PTH) by the perfused rat liver was studied. Labeled hormone, with or without cold hormone, was infused into the circulating perfusion medium containing various calcium concentrations. Pefusate samples at various time periods after the introduction of PTH into the system were chromatographed on Bio-gel P-10; radioactivity and/or immunoreactivity were measured in eluted fractions. Before the perfusion, all immuno- and radioactivity eluted in a single peak, with an apparent mol wt of 9,500 (peak I). After perfusion for 15 min, two other peaks with approximate mol wt of 7,000 (peak II) and 3,500 (peak III) were discernible. Peak I contained both NH2-terminal and COOH-terminal immunoreactivity and was biologically active at all time periods tested. The relative contribution of NH2-terminal and COOH-terminal immunoreactivity to the total immunoreactivity remained constant in this peak throughout the perfusion. In every respect, peak I had the characteristics of intact hormone. At all times, peak II consisted of only COOH-terminal immunoreactivity and was biologically inactive. At early time periods, peak III contained predominantly NH2-terminal immunoreactivity and was biologically active. With time, the relative contribution of NH2-terminal immunoreactivity decreased strikingly while that of COOH-terminal immunoreactivity increased. The three peaks identified in these experiments were analogous in size, biological activity, and immunological characteristics to those we have previously described for fractionated human hyperparathyroid serum. The rate of metabolism of PTH appeared to be regulated by the calcium concentration in the medium. At a high concentration of calcium (greater than 11 mg/100 ml), PTH metabolism was greatly retarded. At a low concentration of calcium (smaller than 5 mg/100 ml), the rate of metabolism was greatly increased. The physiological significance of our observations on the metabolism of PTH by isolated perfused rat liver is not known. However, since such metabolism results in a biologically active fragment, it is suggested that metabolism of intact hormone may be required before full biological expression is possible.
研究了灌注大鼠肝脏对牛甲状旁腺激素（PTH）的代谢。将标记的激素（有或无冷激素）注入含有不同钙浓度的循环灌注介质中。在将PTH引入系统后的不同时间段采集的灌注液样品在Bio-gel P-10上进行色谱分析；测量洗脱组分中的放射性和/或免疫反应性。灌注前，所有免疫反应性和放射性都在一个单一峰中洗脱，表观分子量为9500（峰I）。灌注15分钟后，可分辨出另外两个峰，近似分子量分别为7000（峰II）和3500（峰III）。峰I同时含有氨基末端和羧基末端免疫反应性，并且在所有测试时间段都具有生物活性。在整个灌注过程中，该峰中氨基末端和羧基末端免疫反应性对总免疫反应性的相对贡献保持恒定。在各方面，峰I都具有完整激素的特征。在所有时间，峰II仅由羧基末端免疫反应性组成，且无生物活性。在早期时间段，峰III主要含有氨基末端免疫反应性且具有生物活性。随着时间推移，氨基末端免疫反应性的相对贡献显著下降，而羧基末端免疫反应性的相对贡献增加。在这些实验中鉴定出的三个峰在大小、生物活性和免疫特性方面与我们先前描述的人甲状旁腺功能亢进血清分级分离物中的峰类似。PTH的代谢速率似乎受介质中钙浓度的调节。在高钙浓度（大于11mg/100ml）下，PTH代谢大大延迟。在低钙浓度（小于5mg/100ml）下，代谢速率大大增加。我们关于分离的灌注大鼠肝脏对PTH代谢的观察结果的生理意义尚不清楚。然而，由于这种代谢产生一种生物活性片段，提示在完整激素实现完全生物表达之前可能需要进行代谢。
