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

Jaeger, P; Jones, W.; Clemens, Thomas L.; Hayslett, John P.

doi:10.1172/jci112597

Cited by 78 publications

(26 citation statements)

References 29 publications

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“…In the group treated with a high dose of elcatonin, urinary execration of calcium tended to increase, despite no increases in urinary CTX. This might be a consequence of increased production of 1,25(OH) 2 D 3 and calcium absorption from the intestine, 19 although we did not analyze the serum 1,25(OH) 2 D 3 concentration. The peak levels of urinary CTX in the vehicle-treated mice gradually decreased to the level in the sham-operated mice by day 28, whereas increases in the osteoclast surface in the noninjured femur continued.…”

Section: Discussionmentioning

confidence: 99%

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

Katae

Tanaka

Sakai

et al. 2009

Journal Orthopaedic Research

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It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12-week-old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28-day experiment. Urinary crosslinked C-telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle-treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect.

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Section: Discussionmentioning

confidence: 99%

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

Katae

Tanaka

Sakai

et al. 2009

Journal Orthopaedic Research

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“…In addition, in the absence of calcitonin, serum calcium is unaffected (25). The elevation in plasma 1,25(OH) 2 D 3 in rats treated with calcitonin (11) and the increased serum 1,25(OH) 2 D 3 lev-els in patients with medullary thyroid carcinoma as well as the decrease in 1,25(OH) 2 D 3 levels after surgical cure of medullary thyroid carcinoma and hypercalcitoninemia (24,26) further suggest multiple roles of calcitonin and specifically a direct effect of calcitonin on renal 1␣(OH)ase.…”

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confidence: 95%

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Zhong

Armbrecht

Christakos

2009

Journal of Biological Chemistry

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Although parathyroid hormone (PTH) induces 25-hydroxyvitamin D 3 (25(OH)D 3 ) 1␣-hydroxylase (1␣(OH)ase) underhypocalcemic conditions, previous studies showed that calcitonin, not PTH, has an important role in the maintenance of serum 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) under normocalcemic conditions. In this study we report that 1␣(OH)ase transcription is strongly induced by calcitonin in kidney cells and indicate mechanisms that underlie this regulation. The transcription factor C/EBP␤ is up-regulated by calcitonin in kidney cells and results in a significant enhancement of calcitonin induction of 1␣(OH)ase transcription and protein expression. Mutation constructs of the 1␣(OH)ase promoter demonstrate the importance of the C/EBP␤ binding site at ؊79/؊73 for activation of the 1␣(OH)ase promoter by calcitonin. The SWI/SNF chromatin remodeling complex was found to cooperate with calcitonin in the regulation of 1␣(OH)ase. Chromatin immunoprecipitation analysis showed that calcitonin recruits C/EBP␤ to the 1␣(OH)ase promoter, and Re-chromatin immunoprecipitation analysis (sequential chromatin immunoprecipitations using different antibodies) showed that C/EBP␤ and BRG1, an ATPase that is a component of the SWI/SNF complex, bind simultaneously to the 1␣(OH)ase promoter. These findings are the first to address the dynamics between calcitonin, C/EBP␤, and SWI/SNF in the regulation of 1␣(OH)ase and provide a mechanism, for the first time, for calcitonin induction of 1␣(OH)ase. Because plasma calcitonin as well as 1,25(OH) 2 D 3 have been reported to be increased during pregnancy and lactation and in early development, these findings suggest a mechanism that may account, at least in part, for the increase in plasma 1,25(OH) 2 D 3 during these times of increased calcium requirement.Vitamin D is a principal factor required for maintaining normal calcium homeostasis (1). The active form of vitamin D,3 is generated by two successive hydroxylations; 25-hydroxylation in the liver and 1␣-hydroxylation in the kidney (1-3). Inactivating mutations in the 25-hydroxvitamin D 3 1␣-hydroxylase (1␣(OH)ase) gene result in vitamin D dependent rickets type I despite normal intake of vitamin D, indicating the importance of the 1␣(OH)ase enzyme (4, 5). Elevated parathyroid hormone (PTH) resulting from hypocalcemia is a primary signal mediating the renal synthesis of 1,25(OH) 2 D 3 (6). PTH stimulates 1␣(OH)ase transcription, resulting in increased 1,25(OH) 2 D 3 synthesis (7-9). However, under normocalcemic conditions, PTH fails to stimulate 1␣(OH)ase expression (10). Previous studies showed that calcitonin can enhance renal conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 and that calcitonin, not PTH, is the major regulator of 1␣(OH)ase in the normocalcemic state (10 -13). In early development and during pregnancy and lactation calcitonin levels are increased under normocalcemic conditions and correlated to an increase in serum 1,25(OH) 2 D 3 levels (14 -17). The stimulation of 1,25(OH) 2 D 3 under normocalcemic conditions by calcitonin m...

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“…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.…”

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

Naveh-Many

Silver²

1988

J. Clin. Invest.

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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.

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

Cited by 78 publications

References 29 publications

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

Elcatonin injections suppress systemic bone resorption without affecting cortical bone regeneration after drill‐hole injuries in mice

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

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

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