Salmon calcitonin-induced stimulation of 1α,25-dihydroxycholecalciferol synthesis in rats involving a mechanism independent of adenosine 3′:5′-cyclic monophosphate

Although it is well established that parathyroid hormone and phosphate are important regulators of 1,25-dihydroxyvitamin D 11,25(OH)2D] production, it remains unclear whether calcitonin affects vitamin D metabolism in vivo. Experiments were performed in the rat to determine the effect of chronic calcitonin infusion (0.2 U. h-') on plasma levels of vitamin D metabolites and on calcium metabolism. Thyroparathyroidectomized animals fed a calcium-replete or calcium-free diet were studied for as long as 2 wk before they were killed. In control rats, a calciumfree diet alone for 12 d resulted in an increase in 1,25(OH)2D levels from 24±5 to 139±37 pg * ml-', P = 0.025. The infusion of calcitonin also stimulated 1,25(OH)2D levels compared with controls on a regular diet (80±17 vs. 38±6 pg-ml-', P < 0.05) and on a calcium-free diet (460±50 vs. 139±37 pg -ml-', P < 0.001). In addition, calcitonin increased plasma calcium levels in animals on a regular diet by 50%; this effect was most likely due to increased intestinal absorption of calcium, because removal of calcium from the diet markedly blunted this effect. In contrast, calcitonin administration did not significantly affect 25(OH)D plasma levels. Collectively, these data suggest that calcitonin and calcium are independent regulators of 1,25(0H)2D production and that calcitonin stimulates intestinal absorption of calcium, by increasing circulating levels of 1,25(OH)2D.

Section: Introductionmentioning

confidence: 47%

Evidence that calcitonin stimulates 1,25-dihydroxyvitamin D production and intestinal absorption of calcium in vivo.

Jaeger¹,

Jones²,

Clemens³

et al. 1986

“…(9). Doses and the duration of PTH, cyclic AMP, and calcitonin were those maximally stimulating the la-hydroxylase of the kidney of vitamin D-deficient rats (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Acidosis Suppresses 25-Hydroxyvitamin D3-1α-Hydroxylase in the Rat Kidney

Kawashima¹,

Kraut²,

Kurokawa³

1982

A B S T R A C T Effect of metabolic acidosis on two distinct 25-hydroxyvitamin D3-la-hydroxylase (la-hydroxylase) systems was studied in the kidneys of vitamin D-deficient rats; one is localized in the proximal convoluted tubule (PCT), is activated in vitamin D deficiency, and is regulated primarily by parathyroid hormone (PTH) via cyclic AMP; the other is localized in the proximal straight tubule (PST), is latent in vitamin D deficiency, and is selectively stimulated by calcitonin via a cyclic AMP-independent mechanism. The la-hydroxylase activities were measured in the PCT and PST microdissected from the kidney of vitamin D-deficient rats with or without metabolic acidosis of varying duration. The la-hydroxylase activity decreased in the PCT from 0.74±0.07 fmol/mm per h to 0.24±0.02 at day 3 of metabolic acidosis without a further decline at day 7. Neither metabolic acidosis of 16 h duration nor reduction of the incubation medium pH from 7.4 to 7.0 affected the enzyme activity in the PCT. To examine the underlying mechanisrn for the suppression of la-hydroxylase activity, PTH, cyclic AMP, or calcitonin was given to rats with metabolic acidosis of 3 d duration. Although PTH failed to augment the suppressed la-hydroxylase activity in the PCT, cyclic AMP restored it to the level of control rats. The la-hydroxylase activity in the PST remained undetectable in control rats and in acidotic rats with Received for publication 11 September 1981 and in revised form 3 March 1982. or without PTH or cyclic AMP treatments. However, calcitonin stimulated the la-hydroxylase activity in the PST equally from undetectable to 0.75±0.09 fmol/ mm per h in control and to 0.78±0.10 in acidotic rats. The data suggests that metabolic acidosis suppresses la-hydroxylase only in the PCT by inhibiting PTHdependent adenylate cyclase, and that cellular events beyond cyclic AMP in the PCT and the events responsive to calcitonin in the PST are unaffected. The results show the definite advantage of using defined single nephron segments to study the hormonal and ionic control of the la-hydroxylase system in the kidney.

“…The major regulator of PTH gene transcription both in vitro and in vivo is 1,25(OH)2D3 (1,2). Feedback loops are a characteristic feature of hormone relationships and since calcitonin increases the synthesis of 1,25(OH)2D3 (3)(4)(5) by selectively stimulating the 25(OH)D3 1-hydroxylase enzyme in the proximal straight tubule of rat kidney nephron (6), the question arose whether 1,25(OH)2D3 affected calcitonin production. 1,25(OH)2D3 acts on target cells like classical steroid hormones by binding to stereospecific high affinity receptors that then translocate to the nucleus to affect gene expression.…”

mentioning

confidence: 99%

Regulation of calcitonin gene transcription by vitamin D metabolites in vivo in the rat.

Naveh-Many

Silver²

1988

Calcitonin is secreted by the C cells of the thyroid in response to a raised serum calcium, and acts on bone to lower serum calcium. The C cells have specific receptors for the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. Moreover, calcitonin stimulates the synthesis of 1,25(OH)2D3 in the kidney. Parathyroid hormone (PTH), the third calciotrophic hormone, is also trophic to the renal synthesis of 1,25(OH)2D3, and in turn 1,25(OH)2D3 inhibits PTH gene transcription and synthesis. We report here the marked inhibition of calcitonin gene transcription by the injection of physiologically relevant doses of 1,25(OH)2D3 to normal rats that did not raise serum calcium.Calcitonin mRNA levels after 100 pmol 1,25(OH)2D3 de-creased to 6% of basal at 6 h and 4% at 48 h, and a dose response showed a marked effect even after 12.5 pmol 1,25(OH)2D3, with no appreciably greater effect with larger doses (up to 200 pmol). Control genes, actin, thyroglobulin (thyroid follicular cells), somatostatin (thyroid C-cells) were not affected by 1,25(OH)2D3. Gel blots showed that 1,25(OH)2D3 decreased calcitonin mRNA levels without any change in its size. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' calcitonin transcription was 10% of control, while thyroglobulin and actin were 100%.We propose that calcium is the major regulator of PTH and calcitonin secretion, while 1,25(OH)2D3 is an important regulator of PTH and calcitonin gene transcription. We believe this to be the first demonstration of an effect of 1,25(OH)2D3 on the C cells thereby establishing a new target organ and site of action of vitamin D. Calcitonin is trophic to 1,25(OH)2D3 synthesis, which in turn inhibits calcitonin synthesis, which are the components of a new endocrinological feedback loop.