Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia

Background. Parathyroid hormone-related protein (PTHrP) is now suspected to act as an autocrine or paracrine regulator of cell growth or differentiati on, although it was originally reported as a hypercalcemic substance in mal ignancies. This study was performed to assess the relationship between PTHr P expression and cell proliferation in human parathyroid glands. Methods. The localization of PTH and PTHrP was studied in 42 samples of hyp erplastic parathyroid from 14 long-term hemodialysis cases with immunohisto chemistry and in situ hybridization. Results were compared with proliferati ve activity (proliferating cell nuclear antigen index: counts of proliferat ing cell nuclear antigen-positive cells/100 cells). The localization of the PTH/PTHrP receptor was also examined. Ten normal glands were studied as co ntrols. Results. In hyperplasia, cells positive for PTH, PTHrP, or both were observ ed immunohistochemically. The areas expressing PTHrP mRNA completely coinci ded with those positive for PTHrP immunohistochemically. Oxyphilic or trans itional oxyphilic cells were consistently positive for PTHrP. PTH/PTHrP rec eptors were located in the cytoplasmic membrane in most parathyroid cells. Proliferating cell nuclear antigen-positive cells were rare in normal gland s with an index of 0.22 +/- 0.09 (mean +/- SEM). They were significantly in creased in hyperplastic cases but less for PTHrP-positive than for -negativ e cells (1.25 +/- 0.16 as compared with 7.80 +/- 0.52; P < 0.0001). Conclusion. The observed low level of proliferation of PTHrP-positive cells suggests a functional role for PTHrP as a possible growth suppressor in th e human parathyroid.