Parathyroid cell proliferation in the rat: effect of age and of phosphate administration and recovery.

Abstract

Indirect evidence in human subjects and the low prevalence of mitotic figures in rats suggest that the adult parathyroid gland is a conditional renewal tissue with a low cell birth rate and long cell life span. Accordingly, in normal rats of different ages (8-22 weeks), we measured parathyroid cell and nuclear size, cell number, and gland volume by quantitative microscopy, and cell birth rate and cell life span by Ki-67 expression assuming a duration of expression of 24 h. We also examined the effects of phosphate administration and subsequent recovery. In normal rats, parathyroid volume, cell and nuclear profile area, and cell profile number did not change significantly between 8-22 weeks of age. In younger rats, the calculated cell birth rate was 53.2%/yr, and mean cell life span was 1.9 yr, with a lower 95% confidence limit based on a logarithmic distribution of 6 months. Phosphate loading caused hyperphosphatemia, hypocalcemia, increased PTH secretion, and increased calcitriol production. There was an increase in parathyroid cell and nuclear size consistent with PTH hypersecretion per cell, but a larger increase in cell number and gland volume due to a 3-fold increase in cell birth rate. Six weeks after withdrawal of phosphate administration, cell and nuclear size had fallen to normal, and cell birth rate to half-normal, but cell number and gland volume were even higher. No apoptosis was detected in any gland in any animal, probably because it is short and infrequent, rather than absent altogether. The following conclusions were made. 1) In normal rats, parathyroid cell birth rate is very low, but can be increased by hypocalcemia, establishing the status of the parathyroid gland as a conditional renewal tissue. 2) Despite subnormal cell birth rate, the hyperplasia induced by 8 weeks of phosphate administration could not regress to normal within the animal's remaining life span.