Calcium Regulates Parathyroid Hormone Messenger Ribonucleic Acid (mRNA), but not Calcitonin mRNAin Vivoin the Rat. Dominant Role of 1,25-Dihydroxyvitamin D*

Abstract

In vivo 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) decreased PTH and calcitonin gene transcription. A low calcium is the major signal for PTH secretion, and a high calcium for calcitonin secretion. We report here that calcium has no effect on calcitonin messenger RNA (mRNA) levels in vivo in the rat, but that a low calcium markedly stimulates PTH mRNA levels. Serum calcium was decreased by ip phosphorus and increased by calcium gluconate (ip or iv infusion) and demonstrated that a low serum calcium markedly increased PTH mRNA levels whereas a high serum calcium had no effect. There was no change in mRNAs for calcitonin or actin in the same thyroparathyroid extracts. After phosphorus ip serum calcium decreased from 10.4 to 8.5 mg/dl and PTH mRNA increased up to 3-fold at 1, 3, and 6 h. Gel blots showed that a low calcium increased PTH mRNA levels with no change in its size (833 base pairs). Calcitonin ip decreased both serum calcium and phosphorus with an up to 5-fold increase in PTH mRNA at 1 h, thus demonstrating that the effect of phosphorus on PTH mRNA was due to the low serum calcium and not the high serum phosphorus. When phosphorus and 1,25(OH)2D3 (100 pmol/100 g) were injected together, despite the low serum calcium, there was a decrease in PTH mRNA levels. These results show a linear relationship between calcium and PTH gene expression, but not calcitonin or actin, with a dominant role for 1,25(OH)2D3.

Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.

“…Calcium not only determines PTH secretion but also regulates PTH gene expression both in vitro (1,2) and in vivo (3,4). Calcitonin, on the other hand, is secreted in response to a high calcium but its transcription is not affected by calcium (4).…”

“…Calcium not only determines PTH secretion but also regulates PTH gene expression both in vitro (1,2) and in vivo (3,4). Calcitonin, on the other hand, is secreted in response to a high calcium but its transcription is not affected by calcium (4). The transcription of both PTH and calcitonin genes is markedly reduced by 1,25(OH)2D3 both in vitro (5)(6)(7) and in vivo (8,9), suggesting a central role for 1,25(OH)2D3 in orchestrating calcium homeostasis.…”

Influence of renal function on clinico-pathological features of primary hyperparathyroidism

“…Tomlinson et al (24) showed that the urinary cAMP response to PTH is blunted in patients with HPT and that this phenomenon tends to occur in patients with high endogenous PTH concentrations. Because 1,25(OH) 2 D is required to correct skeletal resistance to the calcemic action of PTH (25), and it inhibits synthesis and secretion of PTH in vitro and in vivo (26,27), reduced 1,25(OH) 2 D promotes proliferation of the parathyroid glands, resulting in a vicious cycle of HPT. We found an increased frequency of multiglandular disease in the renal insufficiency group.…”

Estrogen receptors and biologic response in rat parathyroid tissue and C cells.

“…The PTH gene's expression is also regulated by calcium, where the major effect is that ofa low calcium increasing PTHmRNA levels in vivo (2, 7). In contrast, calcitonin gene expression is not regulated by calcium in vivo (7). At the level of secretion, calcium is the major regulator for both PTH, and calcitonin, with a low calcium being the secretagogue for PTH, and a high calcium for calcitonin.…”