Parathyroid hormone: new assays, new receptors

Accurate measurements of parathyroid hormone (PTH) in plasma are necessary for the assessment, monitoring, and therapy of disorders of bone and mineral metabolism including renal osteodystrophy. Assays for PTH have evolved to provide 2-site immunometric assays that are highly specific for the intact 84 amino-acid peptide, PTH (1-84). With the advent of such assays, it has been shown that the prior generation of assays, thought to measure intact PTH, in fact, also detected a PTH peptide that was truncated at the N-terminus and that appeared to be similar to PTH (7-84). There has been renewed interest in such circulating PTH fragments in view of the demonstration that PTH (7-84) (and other PTH peptides) might have biologic effects. These effects include an action to oppose the calcemic effect of PTH in vivo and to inhibit bone resorption and osteoclast generation in vitro. These effects appear to be mediated by actions of a receptor for PTH peptides with specificity for the C-terminal region of PTH and distinct from the PTH receptor known to be responsible for all of the classic actions of PTH. Although the C-PTH receptor has not yet been cloned, the observations have opened a new field of research in parathyroid physiology. Clinical applications of the assay of such PTH fragments in relation to the amount of circulating PTH (1-84) concentrations are being sought actively as the new PTH assay methodology is applied to the clinical arena and as the biology of the C-PTH receptor and C-terminal PTH fragments are investigated.