Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans

The 1-31 fragment of human PTH [hPTH-(1-31)NH2] has been shown, like hPTH-(1-34), to have anabolic effects on the skeletons of ovariectomized rats when given intermittently, but, unlike hPTH-(1-34), it does so without affecting serum calcium concentrations and does not activate the protein kinase C second messenger pathway in some target cells. To investigate the biochemical responses to hPTH(1-31) in humans, we have directly compared it to hPTH-(1-34) during the course of slow infusions of each. Ten healthy adults, five men and five women, aged 26 +/- 5 yr (range, 22-37), each received 8-h continuous infusions of 8 pmol/kg.h hPTH-(1-34) and hPTH-(1-31) given in random order at least 2 weeks apart. During the infusions there were significant increases in both plasma and urinary cAMP (P < 0.05), but there were no differences in the responses between the two peptides (P = 0.362 for plasma; P = 0.987 for urine). There were also significant phosphaturic and natriuretic responses to the two peptides, which again were not different between peptides. During the infusion of hPTH-(1-34) serum ionized calcium (Ca2+) increased from 1.21 +/- 0.033 to 1.29 +/- 0.046 mmol/L (P < 0.01), and endogenous hPTH-(1-84) decreased from 29.6 +/- 9 to 15.0 +/- 5.7 pg/mL (P < 0.01) such that there was a negative correlation between them (r(2) = 0.45). However, when hPTH-(1-31) was infused, neither serum Ca2+ (1.24 +/- 0.03 us. 1.25 +/- 0.03) nor hPTH-(1-84) (26.8 +/- 5 vs. 30.7 +/- 12 pg/mL) was affected. Circulating concentrations of 1,25-dihydroxyvitamin D-3 increased from 92 +/- 42 to 131 +/- 63 pmol/L (P < 0.05) during infusion of hPTH-(1-34) and from 92 +/- 27 to 110 +/- 42 pmol/L (P = NS) during hPTH-(1-31) infusion. There was also a significant increase in the urinary measure of type I collagen degradation of aminoterminal telopeptides from 78 +/- 45 to 101 +/- 51nmol/mmol creatinine (P < 0.05) when hPTH-(1-34) was infused, but it was not affected (68 +/- 30 us. 66 +/- 24 nmol/mmol creatinine) by hPTH-(1-31). Therefore, hPTH-(1-3) appears to be equivalent and equipotent to hPTH(1-34) in the release of cAMP from target tissues and the renal handling of phosphate and sodium. However, at the doses employed, it does not increase serum calcium, is a weaker stimulator of the 25-hydroxyvitamin D-1 alpha-hydroxylase, and does not induce rapid bone resorption.