A novel parathyroid hormone-related gene product.

A parathyroid hormone-related protein (PTHrP) has been invoked as being responsible for the humoral hypercalcemia of malignancy. Eight of the first 13 amino acids of PTHrP are identical with those in PTH, but there is no other significant homology. The PTHrP gene is located on chromosome 12, whereas that for PTH is on chromosome 11, and the two genes are probably related by a duplication process. Antisera against PTHrP(1-34), which cross-react poorly or not at all with PTH, and antisera against other parts of PTHrP not homologous to PTH were used in immunocytochemistry using a peroxidase-antiperoxidase method, to identify PTHrP in the cytoplasm of cells in a series of unselected parathyroid adenomata. The study was based on our evidence that PTHrP is produced by fetal parathyroid and may be the predominant calcium-regulating hormone in the mammalian fetus. Glands from five patients with parathyroid hyperplasia secondary to chronic renal failure also stained positively for PTHrP. No evidence was obtained for PTHrP in sections from five patients with primary parathyroid chief cell hyperplasia or in a small group of patients with the multiple endocrine neoplasia type 1 or type 2 syndromes.