Metabolism of parathyroid hormone: physiologic and clinical significance

Recent findings concerning the metabolism of parathyroid hormone (PTH) and the heterogeneity, or multiple forms, of circulating PTH have spurred widespread investigation of the nature, origin and physiologic significance of the circulating fragments of PTH.Studies of endogenous PTH in man and cow, and of bovine PTH administered to dogs, have been performed utilizing sensitive, specific immunochemical and radiochemical technics. These studies indicate that fragments of the hormone are responsible for most of the immunoreactive PTH (iPTH) detected in the general circulation and that hormonal cleavage occurs after secretion but not in the intravascular space. Studies of parathyroid effluent plasma have established that the principal secretory product of the parathyroid glands is intact hormone; whether other immunoreactive forms of the hormone are also secreted from the gland is uncertain.In all species studied, the predominant form of circulating hormone is the large fragment consisting of the middle and COOH-terminal portions of the molecule; it lacks more than a third of the NH₂-terminal portion. Because the NH₂-terminal portion of the hormone sequence is required for biologic activity, this large fragment must be biologically inactive.Analysis of cleavage patterns of intact hormone indicates that an NH₂-terminal fragment containing the necessary structural requirements for biologic activity may be produced by this cleavage. This may be of considerable physiologic significance regardless of whether this NH₂-terminal fragment circulates or is present only outside the intravascular space. Although the significance of hormone metabolism is still unclear, the present findings are helpful in the application and interpretation of radioimmunoassays for PTH.