Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha-hydroxylase activity in rodents.
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).(ABSTRACT TRUNCATED AT 250 WORDS)
Walker
A T
AT
Department of Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut 06510.
Stewart
A F
AF
Korn
E A
EA
Shiratori
T
T
Mitnick
M A
MA
Carpenter
T O
TO
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D012016:Reference Values; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase