Direct regulation by calcium of cytoplasmic messenger ribonucleic acid coding for pre-proparathyroid hormone in isolated bovine parathyroid cells.

Abstract

A B S T R A C T DNA complementary to bovine preproparathyroid hormone mRNA was cloned and labeled by nick translation in order to measure mRNA by molecular hybridization. Bovine parathyroid cells were maintained in primary tissue culture for periods up to 96 h at 0.5 mM, 1.25 mM, and 2.5 mM calcium, which was followed by extraction of cellular RNA. Levels of mRNA showed no differences at 0.5 or 1.25 mM calcium, but at high calcium levels, there was a reversible decrease that began at 16 h to a plateau at 30% of control after 72 h. These studies suggest that the glandular capacity to synthesize hormone may be at or near maximal at normal calcium, but at high calcium, there is a decrease over time in steady state levels of mRNA.

The influence of acute and chronic hypercalcemia on the parathyroid hormone response to hypocalcemia in rabbits

“…High levels of extracellular Ca 2+ have been shown to promote intracellular PTH degradation both in vivo (5) and in vitro (4), thus an increase in intracellular PTH metabolism could be a major factor in the reduced PTH response to hypocalcemia found in Group II. Likewise, an elevation in extracellular Ca 2+ concentration has also been shown to inhibit PTH biosynthesis by decreasing levels of PTH mRNA (7,8). However, the decrease in PTH mRNA begins after 16 h of exposure to high Ca 2+ (7) ; therefore changes in PTH synthesis are probably not relevant in our acute (2 h) experiments.…”

“…Likewise, an elevation in extracellular Ca 2+ concentration has also been shown to inhibit PTH biosynthesis by decreasing levels of PTH mRNA (7,8). However, the decrease in PTH mRNA begins after 16 h of exposure to high Ca 2+ (7) ; therefore changes in PTH synthesis are probably not relevant in our acute (2 h) experiments. It has also been speculated that secretory products could modify the PTH response to changes in plasma Ca 2+ .…”

“…It is likely that some of the changes in PTH metabolism that have been described when parathyroid glands are exposed to acute hypercalcemia (4,5) will also be present in chronic hypercalcemia (6). Moreover, chronic hypercalcemia has been reported to influence PTH gene transcription and decrease PTH mRNA levels (7,8). Thus, theoretically, chronic hypercalcemia should also decrease the PTH response to hypocalcemia.…”

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).…”

DISPOSITION AND METABOLISM OF F6-1α,25(OH)2 VITAMIN D3 AND 1α,25(OH)2 VITAMIN D3 IN THE PARATHYROID GLANDS OF RATS DOSED WITH TRITIUM-LABELED COMPOUNDS

“…1␣,25-Dihydroxyvitamin D 3 [1␣,25(OH) 2 VD 3 1 ], the active and hormonal form of vitamin D 3 , is a potent negative regulator of parathyroid gland function, with effects on both PTH mRNA production and PTH secretion as well as parathyroid cell proliferation (Chertow et al, 1975;Mayer and Hurst, 1978;Cantly et al, 1985;Silver et al, 1985Silver et al, , 1986Russell et al, 1986). 26,26,26,27,27,25(OH) 2 vitamin D 3 25(OH) 2 VD 3 ], a fluorinated derivative of 1␣,25(OH) 2 VD 3 has been reported to be several times as potent as the parent compound at increasing intestinal calcium transport and bone calcium (Tanaka et al, 1984;Kiriyama et al, 1991;Inaba et al, 1993).…”