Effect of calcium and magnesium on deoxyribonucleic acid synthesis in rat parathyroid glands in vitro.

DNA synthesis in rat parathyroid glands in organ culture is significantly affected by the calcium concentration of the medium. 3-H-thymidine incorporation over a 46-hour period was more than 100 per cent greater at 1.3 mM calcium than at 3.0 mM calcium. Thymidine incorporation was greatest at 0.9 to 1.3 mM, and fell off sharply between 1.3 and 1.8 mM calcium. Variation of magnesium concentration between 0.3 and 1.5 mM had no appreciable effect on DNA synthesis at either 1.3 or 1.8 mM calcium. No effect on DNA synthesis in rat liver explants or mouse L cells was observed over these ranges of calcium concentration, but in cultured rat kidney fragments, an opposite effect of calcium was observed, i.e., DNA synthesis was more active at 3.0 mM calcium than at 1.3 mM calcium. Time course experiments showed that a significant difference between DNA synthesis rates in high and low calcium media was observable in parathyroid glands during the first 3 hours in culture, and persisted for at least 108 hours. The calcium effect on DNA synthesis was not mediated by any direct effect on the rate of thymidine uptake by the tissue. These results suggest that a small drop in ambient calcium concentration in vivo could significantly increase the rate of DNA synthesis in the parathyroid glands, and thus provide experimental support for the concept that parathyroid hyperplasia in chronic renal insufficiency is caused by lowered serum calcium levels.