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Comparison of the Biochemical Responses to Human Parathyroid Hormone-(1–31)NH₂ and hPTH-(1–34) in Healthy Humans¹

Departments of Medicine (L.J.F., R.A., P.H.W., A.B.H.) and Biochemistry (L.J.F.), The Lawson Research Institute, St. Joseph’s Health Center, University of Western Ontario, London, Ontario, Canada N6A 4V2; the Departments of Medicine and Physiology (G.N.H., J.E.H., K.L.C., D.G.), McGill University, Montreal, Quebec, Canada; and the Institute for Biological Sciences, National Research Council (P.M., G.E.W., J.F.W.), Ottawa, Ontario, Canada

Address all correspondence and requests for reprints to: Dr. Laurence J. Fraher, Room G-442, St. Joseph’s Health Center, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2. E-mail: lfraher{at}lri.stjosephs.london.on.ca

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 (r² = 0.45). However, when hPTH-(1–31) was infused, neither serum Ca²⁺ (1.24 ± 0.03 vs. 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 D₃ 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 amino-terminal telopeptides from 78 ± 45 to 101 ± 51 nmol/mmol creatinine (P < 0.05) when hPTH-(1–34) was infused, but it was not affected (68 ± 30 vs. 66 ± 24 nmol/mmol creatinine) by hPTH-(1–31). Therefore, hPTH-(1–31) 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-hydroxylase, and does not induce rapid bone resorption.

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