The Cytochemical Bioassay for Parathyroid Hormone

Abstract

Although radioimmunoassays represent the standard for measurement of parathyroid hormone (PTH), and their high through-put will continue to ensure their place as the major mode of routine measurement of PTH, increasing knowledge of PTH metabolism and increasing sophistication with radioimmunoassay technology have illuminated the limitations of this mode of assay. Thus, most radioimmunoassays are relatively insensitive and frequently cannot detect circulating levels in normal individuals. Furthermore, none can detect all normal levels and, therefore, no current radioimmunoassay can distinguish normal from hypoparathyroid levels. In part, this relates to the use of heterologous assay systems, frequently employing bovine PTH as a tracer and antiserum to bovine PTH or its fragments in attempting to measure human PTH, although recently successful homologous assay systems have been introduced. Another major factor limiting biological specificity of the radioimmunoassay is the presence in the circulation of chemical forms of the hormone of varying degrees of biological activity and of varying half-lives. Thus, the complex biosynthesis of PTH is known to proceed via precursor forms. Although none has as yet been proven to circulate, such a possibility does exist, and, at least ProPTH is known to have reduced bioactivity. Of more proven importance is the presence in the circulation of middle and carboxyl hormonal fragments which are believed to have no bioactivity and yet have prolonged half-lives relative to the major glandular form of the hormone, PTH(l-84).