Biological Activities of Synthetic Human Parathyroid Hormone (PTH) 1–84 Relative to Natural Bovine 1–84 PTH in Two Differentin VivoBioassay Systems

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Abstract
Synthetic 1-84 human PTH (hPTH) peptides (with either asparagine) or aspartic acid at position 76 were compared with natural bovine PTH (bPTH) in three in vivo bioassays. Surprisingly, in the chick hypercalcemia bioassay, the human 1-84 peptides were approximately 3 times more potent on a molar basis than bPTH. In contrast, in an in vivo mouse kidney cAMP accumulation bioassay, these human peptides were 3-6 times less potent than bPTH. This low potency of synthetic hPTH relative to bPTH in the renal cAMP assay is in accordance with published relative potency estimates for natural extracted hPTH in vitro rat renal membrane adenylate cyclase assays. The human and bovine 1-84 peptides were weakly active in an in vivo mouse calvaria cAMP accumulation system, producing a shallow dose-response curve which was not suitable for any quantitative estimates of potency. In contrast, both human and bovine 1-34 fragments were highly active in stimulating accumulation of cAMP in calvaria thus emphasizing the qualitative differences between 1-84 PTH, they have markedly different quantitative biological effects on hypercalcemia in chicks and in vivo renal cAMP accumulation in mice. Any estimate of the biological potency of human 1-84 PTH, relative to bovine 1-84 PTH, will need to be defined in terms of the nature and species of the biological test system.

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