Response of the Renal Vitamin D Endocrine System to Oxidized Parathyroid Hormone (1-34)

Abstract

Two preparations of bovine parathyroid hormone (bPTH), the natural bPTH(1-84) and the synthetic bPTH(1-34) fragment, have been treated with hydrogen peroxide and assayed for the effect of such treatment on the renal vitamin D endocrine system in Japanese quail. The oxidized and untreated preparations were injected intramuscularly into 4-week-old male Japanese quail, 12 hr after which the kidneys were removed and homogenized. The kidney homogenates were incubated with tritiated 25-hydroxyvitamin D₃[25-(OH)D₃] and the production rates of 1,25-(OH)₂D₃ and of 24,25-(OH)₂D₃ were determined as indices of 25-(OH)D₃-l-hydroxylase and 25-(OH)D₃-24-hydroxylase activities, respectively. Both untreated bPTH(1-34) and untreated bPTH(1-84) stimulated 1-hydroxylase and suppressed 24-hydroxylase activities. Oxidation of either bPTH(1-34) or bPTH(1-84) did not eliminate these responses, whereas the effects of oxidation on other responses to bPTH(1-34), namely inactivation of the hypotensive and renal adenylate cyclase stimulating responses, were observed as anticipated from our earlier observations. The importance of these findings is heightened when viewed in the context of our previous reports that oxidation of bPTH(1-34) leaves the hypercalcemic and hypocalciuric responses intact while partially or possibly totally inactivating all other major responses studied to date. It may be concluded that the mechanisms involved in effecting the hypercalcemic, hypocalciuric, and renal 25-(OH)D₃-1-hydroxylase responses to bPTH(1-34) demand structural requirements in the peptide molecule which are different from those needed to effect the hyperphosphaturic, hypophosphatemic, hypotensive, smooth muscle relaxing, and renal adenylate cyclase responses.