The funcation of parathyroid hormone-related protein.

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The localization of parathyroid hormone(PTH)and PTH-related protein(PTHrP)were studied in 42 hyperplastic parathyroid glands in long term hemodialysis cases with immunohistochemistry and in situ hybridization. Results were compared with proliferaative activity(PCNA index : counts of proliferating cell nucleaar antaigen-positive cells/100 cells)on the same section used for PTH/PTHrP immunostaining. Ten normal glands weree studied as the control.In hyperplasia, cells positive for either PTH or PTHrP,or both, were observed immunohisstochemically. The areas expressing PTHrP mRNA were completely coincided with those positive for PTHrP immunohistochemically. Oxyphil or transitional oxyphil cells were consistently positive for PTHrP and showed a tendency for grouping together. The PCNA positive cells were rare in normal glands with index of 0.22(]SY.+-。[)0.09(mean (]SY.+-。[) SEM). Proliferating cell components were significantly increased in hyperplastic cases and indices for PTHrP positive cells were 1.25(]SY.+-。[)0.16 and tose for PTHrP negative cells were 7.8(]SY.+-。[)0.52. Thus, the proliferative activity in PTHrP positive cells was sgnificantly loweer than their PTHrP negative conterparts in secondary hyperplasia(P<0.0001).PTHrP is now mostly suspected to act as an autocrine or a paracrine substance regulating cell growth or differentiation, although it was originally reported as the hypercalcemic substance in malignancies. On the basis of suppressed cell proliferation in PTHrP positive cells, we suggest a functional role of PTHrP as growth suppresser in the human parathyroid glands.