title: Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans.
abstract: 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 aminoterminal 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-1alpha-hydroxylase, and does not induce rapid bone resorption.
authors.affiliation: Department of Medicine, The Lawson Research Institute, St. Joseph's Health Center, University of Western Ontario, London, Canada. lfraher@lri.stjosephs.london.on.ca
authors.forename: L J
authors.initials: LJ
authors.lastname: Fraher
authors.forename: R
authors.initials: R
authors.lastname: Avram
authors.forename: P H
authors.initials: PH
authors.lastname: Watson
authors.forename: G N
authors.initials: GN
authors.lastname: Hendy
authors.forename: J E
authors.initials: JE
authors.lastname: Henderson
authors.forename: K L
authors.initials: KL
authors.lastname: Chong
authors.forename: D
authors.initials: D
authors.lastname: Goltzman
authors.forename: P
authors.initials: P
authors.lastname: Morley
authors.forename: G E
authors.initials: GE
authors.lastname: Willick
authors.forename: J F
authors.initials: JF
authors.lastname: Whitfield
authors.forename: A B
authors.initials: AB
authors.lastname: Hodsman
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; C102836:parathyroid hormone (1-31)amide, human; D002117:Calcitriol; D002118:Calcium