Comparison of the effects of various lengths of synthetic human parathyroid hormone-related peptide (hPTHrP) of malignancy on bone resorption and formation in organ culture.

Parathyroid hormone-related peptide (PTHrP) has been shown to be the pathogenic agent in humoral hypercalcemia of malignancy (HHM), but the molecular forms that are secreted have not been fully characterized. PTHrP 1-34 has effects similar to parathyroid hormone (PTH), but C-terminal regions of the peptide, such as the 107-139 fragment found to inhibit resorption in a study by Fenton et al (1991), may have other biological activities not shared with PTH. We have compared the effects of the longer forms of recombinant human PTHrP (hPTHrP 1-84, 1-108, and 1-141) with hPTHrP 1-34 and synthetic bovine PTH (bPTH) 1-34 on bone resorption and formation in cultured neonatal mouse calvariae and fetal rat long bones. hPTHrP 1-84, 1-108, and 1-141 were qualitatively similar to hPTHrP 1-34 and PTH 1-34 in stimulating 45Ca release from both neonatal mouse calvariae and fetal rat long bones and in inhibiting the incorporation of [3H]-proline into collagenase digestible protein (CDP) and stimulating the incorporation of [3H]-thymidine (3H-TdR) in neonatal mouse calvariae. However, hPTHrP 1-108 and 1-141 were less potent at stimulating 45Ca release and inhibiting CDP labeling than hPTHrP 1-34, while hPTHrP 1-84 showed an intermediate potency. Since hPTHrP 1-108 and 1-141 were quite similar in potency, the difference cannot be attributed to an inhibitory effect of the 107-139 fragment. All the peptide lengths tested showed similar potency in stimulating [3H]-TdR incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)