AJP - Endocrinology and Metabolism, Vol 258, Issue 2 E297-E303, Copyright © 1990 by American Physiological Society
Effect of parathyroid hormone-like peptides on 25-hydroxyvitamin D-1 alpha-hydroxylase activity in rodents
A. T. Walker, A. F. Stewart, E. A. Korn, T. Shiratori, M. A. Mitnick and T. O. Carpenter
Department of Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut 06510.
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)
