Effect of parathyroid hormone-related peptide supplementation of soy protein formulas in the neonatal pig model

PTH-related peptide (PTHrP) is found in all milks, including human and pig. To define a role for PTHrP in milk, 2-day-old piglets were randomized to receive soy formula devoid of PTHrP or supplemented with 1 nM synthetic PTHrP(1–86) (n = 8 per group). The number of serum samples with detectable PTHrP by immunoassay (Incstar) and radiometric assay (Nichols) was 9 of 33 and 3 of 13 in PTHrP⁻ and 8 of 27 and 3 of 15 in PTHrP⁺ formula-fed piglets and 8 of 14 and 7 of 12 in naturally suckling piglets, respectively. Serum and urine concentrations of calcium and magnesium and total and bone alkaline phosphatase were similar in both groups at 3, 6, 10, and 17 days of age. No differences were seen in bone mineral content of the tibia measured by single-photon absorptiometry (BMC 0.22 + 0.06 and 0.22 + 0.10) or dual x-ray absorption (BMC 1.43 + 0.36 and 1.31 + 0.78) either in vivo or on excised bone or by measurement of Ca, Mg, or P content or total bone ash (1.26 + 0.26 and 1.38 + 0.28 mg). Intestinal histology, serum intestinal alkaline phosphatase, and net absorption and retention of Ca, Mg, and P in balances from age 11–17 days were all similar. As in humans, however, a developmental pattern was seen for phosphorus regulation in both groups. Serum phosphorus (mg/dl) increased between day 3 and days 6 and 10 of age and then fell to published values for 8-week-old suckling pigs at day 17 associated with an increase in urine phosphorus and cyclic AMP excretion. The rise in serum phosphorus from 3 to 6 days was suggestively attenuated in the piglets receiving PTHrP (4.6 + 1.5 in –PTHrP and 2.6 + 1.3 in +PTHrP; p = 0.02 by nonpaired t-test, ANOVA for treatment effect p = 0.14). Thus, although a suggestive early effect of milk PTHrP on phosphorus regulation may be present before the development of full responsiveness to endogenous PTH, no effects could be demonstrated on mineral absorption, renal regulation, or bone mineralization. Because the synthetic PTHrP studied was only 1–86 amino acids, an effect of more distal, carboxyl-terminal, peptides cannot be excluded.