Abstract
The amino-terminal fragments of human PTH [hPTH-(1-34)] and PTH-related peptide [PTHrP-(1-34)] appear to be equipotent in several rodent models. However, continuous i.v. infusions of these peptides to young human volunteers suggested that a 10-fold higher molar dose of PTHrP was required to produce comparable circulating levels of the peptide and biochemical responses similar to PTH. As PTHrP has a wide variety of target tissues in mammalian species and may, therefore, play a paracrine, rather than an endocrine, hormonal role in vivo, we evaluated whether enhanced metabolic clearance of injected PTHrP might explain its apparently reduced potency as a PTH-like hormone. Ten healthy subjects [age, 25 +/- 9 (+/- SD) yr] received in random order either hPTH-(1-34) or hPTHrP-(1-34) given by bolus i.v. injections in a dose of 10.7 nmol. Measurements of plasma immunoreactive peptide indicated a comparable volume of distribution for each, but the apparent t1/2 (8.3 +/- 1.6 min) and plasma clearance (4.0 +/- 1.4 L/min) for hPTHrP were significantly (P < 0.05) accelerated compared to those of hPTH (t1/2, 10.2 +/- 0.5 min; clearance, 2.0 +/- 0.4 L/min). Peak plasma cAMP levels were 9-fold lower in response to hPTHrP (29.5 +/- 19 vs. 190 +/- 63 pmol/L; P < 0.01), and increases in urinary cAMP excretion were 5-fold lower (2.1 +/- 1.1 vs. 11.2 +/- 3.7 nmol/mmol creatinine; P < 0.01). No major differences were observed in the urinary excretion of phosphate, calcium, or sodium between the two peptides. Although hPTHrP-(1-34) has a 2-fold higher MCR than hPTH-(1-34), this may not explain the more than 5-fold lower plasma or urinary cAMP response to PTHrP in humans. The comparable effects of PTH and PTHrP on urinary phosphate, calcium, and sodium may indicate a non-cAMP-dependent pathway for these responses, although the intracellular pool of cAMP generated to either peptide, and thus the local target tissue response, could not be estimated in the present study.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: The Journal of Clinical Endocrinology & Metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.