Circulating PTH molecular forms: What we know and what we don't P. D'Amour  Kidney International  Volume 70, Pages S29-S33 (July 2006) DOI: 10.1038/sj.ki.5001599 Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 1 Composition of circulating PTH in a normal individual (—) and a terminal renal failure patient (- - - -) after high-pressure liquid chromatography (HPLC) separation of serum and analysis of fractions with PTH assays of different specificities. Mid- and C-PTH assays are first-generation PTH radioimmunoassays with epitopes in the C-structure (last 50 amino acids) of human (h) PTH(1–84). The total (T)-PTH assay is a second-generation PTH assay, similar to other intact PTH assays, with an epitope in the region 12–18 of the N structure of hPTH(1–84). Finally, the cyclase-activating (CA) PTH assay is a third-generation assay with a 1–4 epitope. With each generation, PTH assays have become more and more specific (but not exclusive) for hPTH(1–84), the bioactive form of the hormone on the type I PTH/PTHrP receptor. Kidney International 2006 70, S29-S33DOI: (10.1038/sj.ki.5001599) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 2 The biological activity of PTH can no longer be limited to the interaction of hPTH(1–84) with the type I PTH/PTHrP receptor. First, hPTH(1–84) is a minor form of circulating PTH, and other molecular forms, more representative of the C structure of hPTH(1–84) and abundant in the circulation, appear to exert biological effects often opposite to those of hPTH(1–84) through a different, less well-characterized, C-PTH receptor. How these receptors talk to each other is just beginning to be appreciated and constitutes a new field of research. It is likely that new levels of calcium and bone turnover regulation will come out of this research. Kidney International 2006 70, S29-S33DOI: (10.1038/sj.ki.5001599) Copyright © 2006 International Society of Nephrology Terms and Conditions