Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha-hydroxylase activity in rodents

• Published in: The American journal of physiology Vol. 258; no. 2 Pt 1; p. E297
• Main Authors: Walker, A T, Stewart, A F, Korn, E A, Shiratori, T, Mitnick, M A, Carpenter, T O
• Format: Journal Article
• Language: English
• Published: United States 01.02.1990
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Animals; In Vitro Techniques; Kidney - enzymology; Kinetics; Male; Mice; Mice, Inbred C57BL; Parathyroid Hormone - pharmacology; Peptide Fragments - pharmacology; Reference Values; Steroid Hydroxylases - metabolism; Structure-Activity Relationship
• ISSN: 0002-9513
• DOI: 10.1152/ajpendo.1990.258.2.E297

The role of vitamin D metabolism in the humoral hypercalcemia of malignancy syndrome (HHM) is unclear. We studied in vivo and in vitro effects of synthetic parathyroid hormone-like peptides (PTH-LPs) on rodent renal 25-OHD-1 alpha-hydroxylase activity. Infusion of mice with PTH-LP-(1-36) at 10 pmol/h for 12 and 24 h showed significant (429 +/- 139% and 937 +/- 413%, respectively) stimulation of control enzyme activity. Infusion for 36 h demonstrated diminution of activity to levels nearer to the unstimulated state (228 +/- 36% of control). In that maximal activity was observed after 24 h of infusion, we examined 1 alpha-hydroxylase activity after variable dosages of PTH-LP-(1-36) at this time point. Animals infused with PTH-LP-(1-36) at dosages of 2.5, 10, and 30 pmol/h for 24 h demonstrated 1 alpha-hydroxylase activities of 0.71 +/- 0.12, 4.74 +/- 2.09, and 9.91 +/- 1.01 ng.mg protein-1.20 min-1 (means +/- SD), respectively, all significantly greater than control activity (0.51 +/- 0.20 ng.mg protein-1.20 min-1). PTH-LP-(1-36) and PTH-LP-(1-74) were comparable in potency to bovine (b)PTH-(1-34) in stimulating 1 alpha-hydroxylase. Direct in vitro incubation of PTH-LP-(1-36) with renal slices resulted in stimulation of 1 alpha-hydroxylase activity up to 200% of control levels, comparable to that seen with equimolar concentrations of bPTH-(1-34).