Phosphate administration increases both size and number of parathyroid cells in adult rats

Phosphate administration increases both parathyroid hormone (PTH) secretion and parathyroid size in rats, but the relative contribution of hypertrophy and hyperplasia is unknown. Accordingly, we reexamined parathyroid histology in a previously published experiment [6], quantitatively rather than qualitatively. Ninety female Long-Evans rats were divided into six groups; three were given a normal diet, and three a high phosphate diet (Ca/P 1:7). One group from each arm was killed after 1, 2, and 3 months. Quantitative microscopy was performed on the parathyroid section with the largest area from each animal, without knowledge of its experimental status. Total gland area and total number of cell profiles did not change significantly in the control rats, but increased progressively in the phosphate-loaded rats. At 3 months, the difference was +194% for gland area and+151% for profile number (P < 0.0001), much more than could be accounted for by suppression of apoptosis. Mean nuclear profile area and mean cell profile area (including associated connective tissue as well as cytoplasm) were both significantly increased at 1 month (P < 0.0001). The differences persisted, but their magnitudes (about +16%) did not change further. This time course was consistent with the morphologic expression of increased PTH secretory activity. We conclude that phosphate administration to adult rats increases both size and number of parathyroid cells, the latter due to increased cell proliferation. Phosphate-stimulated parathyroid growth could be due to either hypocalcemia or decreased calcitriol production; increased cell division may also be linked to increased hormone secretion, regardless of its cause. The relative importance of these different mechanisms remains to be determined.